Food and Bioprocess Technology (2020) 13:1261–1279
https://doi.org/10.1007/s11947-020-02461-6
REVIEW
Production, Properties, and Applications of α-Terpineol
Adones Sales 1,2
&
Lorena de Oliveira Felipe 3
&
Juliano Lemos Bicas 1
Received: 16 January 2020 / Accepted: 14 May 2020 / Published online: 29 May 2020
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
α-Terpineol (CAS No. 98-55-5) is a tertiary monoterpenoid alcohol widely and commonly used in the flavors and fragrances
industry for its sensory properties. It is present in different natural sources, but its production is mostly based on chemical
hydration using α-pinene or turpentine. Moreover, many bioprocesses for the microbial production of α-terpineol via biotransformation of monoterpenes (limonene, α- and β-pinenes) are also available in the literature. In addition to its traditional use, αterpineol has also been evaluated in other application fields (e.g., medical), since some biological properties other than aroma,
such as antioxidant, anti-inflammatory, antiproliferative, antimicrobial, and analgesic effects, among others, have been attributed
to this compound. Therefore, this review presents an original compilation of data regarding the production (extraction directly
from nature; chemical synthesis; via biotechnological process), the chemical and biological properties, and the current market and
novel applications of α-terpineol to guide further research in this area. Considering the information presented, we believe that αterpineol applications may transcend the flavors and fragrances industry in the future.
Keywords Aroma . Bioactivity . Bioflavor . Fragrance . Terpene
Introduction
Terpineols (C10H18O) are monocyclic monoterpenoid tertiary
alcohols. The structure of terpineol was determined in the
1880s through studies conducted by Semmler, Tiemann,
Wagner, and Wallach, and some years later, its chemical synthesis was accomplished for the first time (Sell and Pybus
2006). Terpineols are recognized as a set of four isomers:
α-, β-, γ-, and δ-terpineol (Fig. 1). The first isomer is widely
found in natural sources (Surburg and Panten 2016) and can
be obtained by fractional distillation from more than 150 essential oils (Burdock 2010). In contrast, β-, γ-, and δterpineol are not widely found in nature.
* Juliano Lemos Bicas
jlbicas@gmail.com
1
2
3
Department of Food Science, School of Food Engineering,
University of Campinas, Rua Monteiro Lobato, 80, Campinas, São
Paulo 13083-862, Brazil
In addition to the traditional uses of α-terpineol, i.e., in the
flavors and fragrances industry, studies in the last few years
have reported multiple biological properties (antioxidant, antiinflammatory, anticonvulsant, antimicrobial, anticarcinogenic, etc.) associated with this compound, as will be presented in
this text. These findings, together with novel biotechnological
methods for producing α-terpineol in hundred-gram-per-liter
yields (including enantiomeric pure forms) (Bicas et al. 2010;
Molina et al. 2019), have led to some new possibilities for
research and development, both in academia and in the industry. As a consequence, the number of documents related to the
keyword “alpha-terpineol” in Scopus has constantly increased
in the last 40 years, particularly in the last 20 years (Fig. 2).
Therefore, the objective of this review is to present the most
relevant scientific advances related to α-terpineol, particularly
those regarding its production strategies and biological
properties.
Occurrence and Production
Grupo Boticário, Centro de Pesquisa e Desenvolvimento, Núcleo de
Avaliação e Soluções Analíticas, Rua Alfredo Pinto, 325, São José
dos Pinhais, Paraná 83050-320, Brazil
Natural Occurrence
Graduate School of Life and Environmental Sciences, University of
Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-0006, Japan
In nature, α-terpineol has been identified in hundreds of
sources (flowers, herbs, leaves, fruits, oils, and others), being
1262
Food Bioprocess Technol (2020) 13:1261–1279
Fig. 1 Structures of α-terpineol
(a), S-(−)-α-terpineol (a1), R(+)-α-terpineol (a2), β-terpineol
(b), γ-terpineol (c) and δ-terpineol
(d)
(a)
(a1)
present in wide-ranging concentrations. Its ester (terpinyl acetate) is also found in different essential oils (cypress, Malabar
cardamom, cajeput, niaouli, Siberian pine needles, pine,
Melaleuca trichostachya, Melaleuca pauciflora, and bitter orange), among other sources (Burdock 2010). Table 1
140
Number of documents
120
100
80
60
40
20
0
1960
1970
1980
1990
Year
2000
2010
2020
Fig. 2 Number of documents related to the keyword “alpha-terpineol” in
Scopus (www.scopus.com) between 1960 and 2019
(b)
(a2)
(c)
(d)
summarizes the main sources of α-terpineol as well as its
percentage of essential oil or other plant-derived fractions.
Table 1 shows that α-terpineol is the main component in
the essential oils (%, w/w) of Marjoram (Origanum majorana,
73%), Pinus pinaster (67.3%), clary sage (Salvia sclarea,
47.4%), Thymus caespititius (32.1%), and Trembleya
parviflora (16.5%), being also the main component of the
absolute of Narcissus poeticus (23.7%). It is also present in
relatively high concentrations (> 1%) in the oil fraction of
other kinds of sources. In these cases, the total amount of αterpineol in the original matrix is in the range of hundreds to
thousands parts per million (ppm) (see Table 1).
α-Terpineol may be present in two enantiomeric forms,
i.e., S-(−)- and R-(+)-α-terpineol (Fig. 1). Although it is
claimed that S-(−)-α-terpineol is the most abundant form
found in nature (Surburg and Panten 2016), Ravid et al.
(Ravid et al. 1995) found that R-(+)-α-terpineol was the predominant enantiomer in most of the 41 essential oils recovered
in laboratory. Enantiomerically pure R-(+)-α-terpineol was
identified in a sample (Micromeria fruticosa (L.) Druce oil),
while high enantiomeric purities of this isomer were detected
in the oils of Origanum vulgare (88%), cardamom (87%),
Food Bioprocess Technol (2020) 13:1261–1279
Table 1
1263
Natural sources in which α-terpineol is the main component or is present in percentages higher than 1% (m/m) in the oily fraction
Source
α-Terpineol in
sample (%, m/m)1
Artemisia rupestris
10.09 in EO
0.21
211
Liu et al. (2013)
Bigarade
Cajeput
11.7 in leaves EO
10.3 in EO
0.6
3.66*
702
3770
(Boussaada and Chemli (2006)
Ravid et al. (1995); Sakasegawa et al. (2003)
Cardamom
5.8 in EO
1.9*
1102
Chandran et al. (2012); Ravid et al. (1995)
Sample in
Estimated amount of Reference
matrix (%, v/m) α-terpineol in the
matrix (ppm)3
*
Cinnamon
10 in bark oil
0.9
900
Kong et al. (2007); Wong et al. (2014)
Clary sage (Salvia sclarea)
47.4 in EO2
1.9
9006
Peana et al. (1999)
Eucalyptus spp.
12.1 in EO
0.6
726
Dagne et al. (2000)
Guava plant
38.7 in leaves EO
0.09
348
de Lima et al. (2010)
Juniperus communis
14 in EO
1.43*
2002
Carroll et al. (2011); Milojević et al. (2008)
Lavandin
2.5 in EO
5.4
1350
Périno-Issartier et al. (2013)
Lemon
4.6 in EO
0.21*
97
Ferhat et al. (2007); Nasser AL-Jabri and
Hossain (2014)
Lime
17.1 in peels EO
5.45*
9320
Atti-Santos et al. (2005); Chisholm et al. (2003)
*
Mentha citrate
4.2 in EO
1.1
462
Malizia et al. (1996); Ravid et al. (1995)
Melaleuca alternifolia
12.04 in leaves EO
5.8*
6983
An et al. (2019); Whish and Williams (1996)
Micromeria fruticosa
2–5 in EO
3 in EO
5.8*
2.3*
1160–2900
690
(ISO 4730 (2017); Whish and Williams (1996)
(Putievsky et al. (1996); Ravid et al. (1995)
Myrcia lundiana
8.41 in leaves EO
1.24
1043
Alves et al. (2018)
0.25
593
Ehret et al. (1992)
*
598
Khodabakhsh et al. (2015); Ravid et al. (1995)
2490
Ireland et al. (2002); Monti et al. (2002)
Narcissus poeticus (absolute of) 23.7 in EtOH extract2
Neroli
4.6 in EO
Niaouli
8.3 in EO
1.3
3*
Nutmeg (Myristica fragrans)
3.1 in seeds EO
6.85
2124
Muchtaridi et al. (2010)
Origanum majorana
73 in EO2
7.7*
56,210
Baser et al. (1993); Novak et al. (2008)
Origanum vulgare
7.6 in EO
1.28
973
Cleff et al. (2010)
Petitgrain
4.9 in EO
1.3*
637
Boussaada and Chemli (2007); Ravid et al. (1995)
Pinus pinaster (pine)
67.3 in oil2
0.61*
4105
Jirovetz et al. (2005); Mimoune et al. (2013)
Satureja montana
2.6 in EO
0.9
234
Prieto et al. (2007)
Tarchonanthus camphoratus
13.2 in EO
0.2
264
(Matasyoh et al. (2007)
*
11 in EO
0.2
220
Ravid et al. (1995)
Thymus caespititius
32.1 in EO2
0.5
1605
Miguel et al. (2004)
Trembleya parviflora
16.5 in EO2
0.02
33
Farias et al. (2018)
1
EO essential oil
2
α-terpineol is the main component in sample
3
Calculated
*
Essential oil yield value obtained in an alternative reference with similar extraction process
Origanum syriacum (84%), Mentha citrata (69–81%),
Artemisia arborescens (80%), and Achillea fragrantissima
(78%). In contrast, the highest enantiomeric purities of
S-(−)-α-terpineol (80%) were evidenced for both cinnamon
and Laurus nobilis oils, while lower purities of this isomer
were observed for the oils of Mentha longifolia (69%), lemon
(67%), Israelian geranium (64%), and cembra pine (64%).
Nearly racemic mixtures (enantiomeric purity < 60%) were
detected in the oils of cubeb (58% R-(+)-α-terpineol),
Origanum majorana (57.5% R-(+)-α-terpineol), sweet marjoram (57% R-(+)-α-terpineol), petitgrain (57% R-(+)-α-terpineol), star anise (57% R-(+)-α-terpineol), tansy (57% R-(+)-αterpineol), cajeput (57% R-(+)-α-terpineol), coriander (52%
R-(+)-α-terpineol) Moroccan and Bourbon geranium (53–
54% S-(−)-α-terpineol), and juniper wood (58% S-(−)-α-terpineol) (Ravid et al. 1995). However, in this study, only two
oil samples (Tarchonanthus camphoratus and cajeput) presented more than 10% of α-terpineol (Table 1).
1264
Other authors reported that R-(+)-α-terpineol was also the
major enantiomer in mango (68.6%), while the opposite occurred for litchi (89% S-(−)-α-terpineol), and a racemic mixture was found in yellow passion fruit (Werkhoff et al. 1993)
as well as in commercial geranium oils (Kreis and Mosandl
1993). In the composition of the essential oil of pistachio
(Pistacia vera), α-terpineol was a minor component (0.2%),
but it was present as enatiomerically pure S-(−)- α-terpineol
(Tsokou et al. 2007).
In terms of commercial production, despite this widespread
occurrence of α-terpineol and its possible recovery from these
natural sources (e.g., by fractional distillation of pine oils), this
component is usually prepared by chemical synthesis (see
below) (NPCS Board of Consultants and Engineers 2010;
Surburg and Panten 2016).
Food Bioprocess Technol (2020) 13:1261–1279
using a phosphoric:acetic acid mass ratio of 1:3 resulted in a
maximum yield of α-terpineol of 20.2% (mol/mol). The reaction mixture also included 34.4% remaining α-pinene and
other side products, such as δ-carene (15%, mol/mol), δlimonene (8.3%), β-pinene (7.5%), α-terpinene (6.7%), camphene (3.8%), and terpin hydrate (0.7%,) (Prakoso et al.
2018). α-Terpineol was also produced from Indonesian turpentine (as mol/mol: 65–85% α-pinene; 1–3% of β-pinene; <
1% camphene; 10–18% 3-carene; 1–3% limonene) by hydration catalyzed by H3PO4 or P2O5-natural zeolite, the former
being preferred to obtain higher yields. When H3PO4 10%
was used as a catalyst in a 8-h reaction, α-pinene was still
the major product (53.48%) found in the reaction mixture,
while α-terpineol (20.43%) was produced together with minor
amounts (1–5%) of other by-products (limonene, camphene,
and terpinolene) (Wijayati et al. 2019).
Chemical Synthesis
Biotechnological Production
The data presented in Table 1 indicate that this compound is
usually present in low concentrations in plants (generally less
than 10,000 ppm, i.e., 1%), even in those whose oily fraction
has α-terpineol as the main component. Moreover, extraction
from natural sources is influenced by the availability of the
starting material, and the composition of essential oils suffers
from seasonal conditions (Farias et al. 2018; Gad et al. 2019).
This information explains why chemical synthesis is the main
method to obtain commercial α-terpineol, even though it is
widely found in natural sources. Thus, recovery from essential
oils is possible, e.g., by fractional distillation of pine oils, but
only minor amounts are supplied by this method (Surburg and
Panten 2016). To give a rough estimation, a flavors and fragrances company (confidential) informed that about 5% of its
α-terpineol comes from natural sources, while the rest has a
chemical origin (personal communication).
The classical chemical process to produce α-terpineol
involves the hydration of α-pinene or turpentine crude oil
with aqueous mineral acid (Fig. 3). In such conditions,
other products may be produced, such as terpin hydrate,
but this compound may be easily converted into the desired product (α-terpineol) by partial dehydration (Sell
2006; Surburg and Panten 2016). A patent description
reports that this method may reach 65% (based on αpinene charged) to 72% (based on α-pinene used) yield.
The main products in the volatile fraction were, besides
α-terpineol, residual α-pinene and monocyclic monoterpenes (Richard and Murray 1958).
Other processes using 3-carene, limonene, pinene, and pentane tricarboxylic acid, for example, may also be applied to the
synthesis of this compound (Burdock 2010; Surburg and
Panten 2016). Recently, other processes for α-terpineol synthesis have been reported. In one of them, the acid-catalyzed
hydration of α-pinene (purity > 97.5%) in only a one-stage
hydration reaction mechanism carried out at 75 °C for 8 h
There are several reports in the literature describing the biotechnological production of α-terpineol, mostly based on the
biotransformation of its monoterpene counterparts (limonene,
α- and β-pinenes) (Fig. 4) (Bier et al. 2017; Noma and
Asakawa 2010; Noma and Asakawa 2015; Vespermann
et al. 2017).
Limonene (C10H16) is a monoterpene found in two enantiomeric forms: R-(+)- and S-(−)-limonene. The enantiomer
R-(+)-limonene is the main component (> 90%) of orange peel
oil and is therefore a cheap by-product commercially available
in large amounts mainly from the citrus industry. Brazil, for
instance, the major citrus producer worldwide, exported in
2018 US$ 403.4·10 6 of R-(+)-limonene-containing byproducts (772.7·103 kg of d-limonene, 21.0·106 kg of terpenes
from the deterpenation process and 29.0·106 kg of orange
essential oil), yielding average FOB prices of US$ 6.6 to 8.9
per kg, depending on the by-product (Brazilian Ministry of
Industry, Foreign Trade and Services 2019). Consequently,
this compound is considered a suitable starting material for
biotransformations (Jongedijk et al. 2016; Sales et al. 2018).
In fact, R-(+)-limonene is the main substrate employed in
biotransformation studies to produce α-terpineol (Tables 2
and 3).
The first report on the biotransformation of limonene for
the production of α-terpineol was described in 1969, in which
the fungus Cladosporium sp. was reported to accumulate
1 g L−1 of product (Kraidman et al. 1969). Since then, several
other studies have been published using fungi or bacteria
(Tables 2 and 3).
The biotransformation of limonene by Sphinghobium sp.
resulted in one of the highest α-terpineol concentrations ever
described for its biotechnological production. Both R-(+)- and
S-(−)-limonene could be specifically converted to R-(+)- and
S-(−)-α-terpineol, respectively. After approximately 100 h of
Food Bioprocess Technol (2020) 13:1261–1279
1265
Fig. 3 Chemical synthesis of αterpineol by the acid-catalyzed
hydration of α-pinene (Sell 2006)
H+
+
H+
H 2O
α-pinene
α-terpineol
biotransformation, almost 130 g L−1 R-(+)-α-terpineol was
produced using a biphasic medium consisting of an aqueous
phase (biomass resuspended in phosphate buffer) and sunflower oil—which accumulated both substrate and product
(Bicas et al. 2010). After optimizing this bioprocess, nearly
240 g L−1 of R-(+)-α-terpineol could be produced from R-(+)limonene in the following conditions: initial substrate (R-(+)limonene) concentration of 350 g per liter of organic phase,
biomass concentration of 2.8 g per liter of aqueous phase,
organic:aqueous phase proportion of 1:3, and incubation at
28 °C/200 rpm for 96 h. However, the yield of α-terpineol
in terms of biomass was more than three times greater when an
aqueous:organic ratio of 1:1 was employed (65 g/g), compared with 1:3 (29 g/g) (Molina et al. 2019). Using this approach, the biotransformation of R-(+)-limonene resulted in a
product with 94.5% R-(+)-α-terpineol, 2.8% S-(−)-α-terpineol, and 2.7% residual substrate, while the biotransformation of
S-(−)-limonene yielded 64.6% S-(−)-α-terpineol, 33.9% R-(+
)-α-terpineol, and 1.5% residual substrate. The estimated enantiomeric excess (ee) of these products (94.2% for the R form
in the former case and 31.5% for the S form in the latter case)
are much better than the values found for commercial αterpineol standards, such as Aldrich’s α-terpineol (90%, technical grade, CAS 98-55-5, Cat. number 432628) and Fluka’s
(+)-α-terpineol (≥ 97%, CAS 7785-53-7, Cat. number 83073)
with an ee of 16% (for the S-(−)- isomer) and 30% (for the
R-(+)-isomer), respectively (Sousa et al. 2020). These studies
indicate that the potential economically feasible biotechnological processes for the production of α-terpineol are available
and also that the enantiospecificity of such a process may be
useful to generate enantiomerically enriched products. This
fact is essential when studying the bioactivities associated
with α-terpineol (see the “Biological Properties” section).
Alpha- and β-pinenes (C10H16) are bicyclic monoterpene
substrates that, besides limonene, are usually employed in
microbial biotransformations to produce α-terpineol
(Tables 2 and 3). These compounds are found in wide range
concentrations in more than 400 essential oils from natural
sources (Burdock 2010). However, the main source of pinenes
is the oil obtained from the distillation of conifers—called
turpentine—which contains about 70% of α-pinene and
25% of β-pinene (Yoo and Day 2002). Similarly to limonene,
α-pinene is considered a relatively inexpensive and abundant
substrate for bioconversion routes (Felipe et al. 2017;
Vespermann et al. 2017). Regarding the biocatalysts for the
biotransformation process of α- and β-pinenes, Absidia
corulea, Aspergillus sp., Aspergillus niger, Candida
tropicalis, Polyporus brumalis, Pseudomonas sp., and
Serratia marcescens are reported in the scientific literature
(as detailed in Tables 2 and 3).
Fig. 4 Microorganisms described in the scientific literature that are capable of converting monoterpenes (R-(+)-limonene, S-(−)-limonene, α-pinene and
β-pinene) into α-terpineol. For further details, refer to Tables 2 and 3
1266
Table 2 Bacterial production of
α-terpineol by the biotransformation of different monoterpene
substrates (R-(+)-limonene, S-(−)limonene, α-pinene and βpinene)
Food Bioprocess Technol (2020) 13:1261–1279
Microorganism
Process details
R-(+)-Limonene as substrate
Escherichia coli
α-Terpineol and carvone production (after 72 h): 215 and
EC423
23 mg L−1 (40 °C); 235 and 35 mg L−1 (50 °C); 209 and
28 mg L−1 (60 °C), respectively. E. coli was genetically
modified.
Pseudomonas gladioli
After 96 h, the production reached 702 ppm (mg L−1) for
α-terpineol and 1861 ppm for perillic acid. Conical flasks
(250 mL) prepared adding 50 mL mineral salts medium at
pH 6.5 + 10 mL inoculum + 1% (v/v) limonene. P. gladioli
was isolated from pine bark and sap.
Pseudomonas
After 30–40 h, the α-terpineol production was equal to
fluorescens NCIMB
10–11 g L−1 either crude enzymatic extract or fresh cells.
Experiment carried out in biphasic medium (organic phase:
11671
n-hexadecane added with 40 g L−1 of (R)-(+)-limonene +
fresh cells or crude enzymatic extract of P. fluorescens.
Sphingobium sp.
Production of (R)-(+)-α-terpineol up to 130 g L−1 after
100–150 h. Bioconversion occurred in conical flask
(250 mL), in biphasic medium (organic phase: sunflower oil +
aqueous phase: frozen Sphingobium sp. cells) – at 30 °C,
200 rpm.
S-(−)-Limonene as substrate
Sphingobium sp.
Production of (S)-(−)-α-terpineol 10–11 g L−1 after 125–150 h.
Bioconversion carried out in conical flask (250 mL), in
biphasic medium (organic phase: n-hexadecane + aqueous
phase: fresh Sphingobium sp. biomass).
α-Pinene as substrate
Pseudomonas sp. PIN
Production of p-cymene (~ 135 mg L−1 after 24 h), α-terpineol
(~ 39 mg L−1, ~ 36 h), α -terpinolene (~ 30 mg L−1, ~ 18 h),
limonene, and borneol (both, ~ 20 mg L−1, ~ 24 h). Minor
compounds: camphor, α-terpinen-4-ol, and p-cymene-8-ol
and p-menthene derivatives. Conical flasks (500 mL) containing: 20 mL inoculum + 80 mL mineral medium + 1%
(v/v) α-pinene.
Serratia marcescens
S. marcescens was isolated from activated sewage sludge. When
the nitrogen source was altered from 1 g L−1 NH4Cl to
1 g L−1 KNO3 and 10 g L−1 glucose was added as
supplement carbon source, S. marcescens produced
α-terpineol as the major product instead of trans-verbenol.
β-Pinene as substrate
Pseudomonas sp. PIN
Production of p-cymene (~ 200 mg L−1 after 24 h), α
-terpinolene (~ 100 mg L−1, ~ 24 h), α-terpineol and limonene (both, ~ 60 mg L−1, ~ 24 h), and borneol (~ 25 mg L−1,
~ 36 h). Minor compounds: fenchyl alcohol, α-terpinen-4-ol,
and p-cymene-8-ol and p-menthene derivatives. Conical flasks
(500 mL) containing: 20 mL inoculum + 80 mL mineral medium + 1% (v/v) β-pinene.
Table 3 also shows that fungi are the main biocatalyst
involved in biotransformations for the biotechnological
production of α-terpineol. In this case, the prevalence of
fungi to achieve success in biotransformation processes
can be explained by considering the secretome of this type
of microorganisms. Secretome in fungi cells shows the
ability to produce several enzymes that are capable of
degrading different terpene compounds into their derivatives (Alfaro et al. 2014; de Carvalho 2016). Moreover,
according to Abraham et al. (Abraham et al. 1985), fungi
Reference
Savithiry et al.
(1997)
Cadwallader
et al. (1989)
Bicas et al.
(2008b)
Bicas et al.
(2010)
Bicas et al.
(2008a)
Yoo et al.
(2001)
Wright et al.
(1986)
Yoo et al.
(2001)
are more prone to accumulate metabolic intermediates instead of bacteria. From this point of view, bacteria show a
more active metabolism, destroying the substrate more
quickly rather than accumulating the metabolic intermediates of interest (Abraham et al. 1985).
Biotechnological production of α-terpineol also may be
accomplished using de novo synthesis (biosynthesis).
This relates to the production of substances from simple
building block molecules, which are processed by organisms through an entire metabolic pathway to form a
Food Bioprocess Technol (2020) 13:1261–1279
1267
Table 3 Fungal production of α-terpineol by the biotransformation of different monoterpene substrates (R-(+)-limonene, S-(−)-limonene, α-pinene
and β-pinene)
Microorganism
R-(+)-Limonene as substrate
Cladosporium sp.
Process details
Cladosporium sp. was isolated from soil soaked in terpenes and minerals containing d-limonene Kraidman et al.
as sole carbon source. The strain was able to convert d-limonene to 1 g L−1 of α-terpineol.
(1969)
Production of 587.6 mg L−1 α-terpineol after 48 h, in addition to (in mg L−1) carvone (127.71),
terpinen-4-ol (30.14), limonene-1,2-diol (107.55), cis-carveol (133.14), and trans-carveol
(102.38), all of these after 144 h. Optimal conditions: mycelial suspension in 50 mL of potato
dextrose agar (PDA) containing 400 μL of R-(+)-limonene (1%) at 30 °C. The bark of Pinus
taeda was used to obtain the fungus strain.
Fusarium oxysporum 152B
Production of ~ 450 mg L−1 after 72 h. Two agro-residues were applied to the fermentation
process: cassava wastewater for fungal growth, and orange essential oil as an alternative
substrate (R-(+)-limonene) source.
Fusarium oxysporum 152B
Production was optimized to reach ~ 2.4 g L−1 after 72 h. Cultivation conditions: distilled water
added with 0.5% (v/m) R-(+)-limonene +0.25 (m/m) for inoculum/culture medium ratio cultivated at 26 °C and 240 rpm.
Penicillium digitatum CMC 93.24% yield of (R)-(+)-α-terpineol (ee > 99%) and 0.96% of non-converted limonene.
P. digitatum was isolated from spoiled mandarin. The best result was achieved when ethanol
was applied as solvent in 0.6 (v/v) in liquid broth.
Penicillium digitatum NRRL Production of 12.83 mg (g beads)−1 day−1 with 45.81% bioconversion of substrate. Optimum
conditions obtained in continuous feed (limonene, Tween 80 and citrate/phosphate buffer) in
1202
air lift bioreactor were 500 mL of reaction volume, 0.3 slpm of aeration rate, 0.0144 h −1 of
dilution rate, 150 g immobilized calcium alginate beads, 1% (v/v) limonene + 1% (v/v) Tween
80 in sterile 0.01 M citrate/phosphate buffer (pH 7.0).
Penicillium digitatum NRRL Production of 3.2 mg L−1 after 24 h. Fermentation process optimum conditions: limonene = 1%
(v/v), pH 4.5, 28 °C. Oxygen requirement = 1.6 mg mL−1. Substrate induction prior to
1202
biotransformation.
Penicillium digitatum NRRL Cold-pressed orange peel oil containing 96.1% of limonene was applied as substrate. Substrate
1202
fed-batch and the media Malt Yeast Broth (pH 6.1) and Malt Extract Broth (pH 5.4) were used.
After the second substrate addition and cultivation at 25–27 °C for 31 h, the selectivity for the
α-terpineol was 67.7% (w/v) in MYB and 47.1% in MEB.
Penicillium digitatum DSM Production of 833.93 mg L−1 by resting cells of P. digitatum after 12 h. Optimal conditions were
24 °C, 150 rpm, pH 6.0, 84 mg L−1 of limonene (added in the beginning of fungal log phase),
62840
followed by 840 mg L−1 of limonene (selectivity above 99%) in ethanol as co-solvent added in
48 h pre-culture medium in mid log phase.
Penicillium digitatum DSM (R)-(+)-α-Terpineol (67.2%, w/v), cis-p-menth-2-en-1-ol (1.27), trans-p-menth-2-en-1-ol (0.68),
62840
neo-dihydrocarveol (1.70), and cis-limonene oxide (0.29) were obtained after 8 h when
50 μL mL−1 R-(+)-limonene was added (as a 20% solution in ethanol) in 50 mL of submerged
liquid culture inoculated with 0.5 mL of fresh spore suspension containing 9.9 × 107 spores
mL−1.
Yeast (code 05.01.35)
The yeast 05.01.35 was isolated from orange juice industry residue from the south of Brazil.
Production of 1700 mg L−1 of α-terpineol was achieved when 2 g of biomass (inoculum) was
cultivated for 144 h at 30 °C and 175 rpm in the presence of 1.75% substrate (as 1:1 ethanol
mixture).
S-(−)-Limonene as substrate
Penicillium digitatum DSM (S)-(−)-α-Terpineol (16.97%, w/v), cis-p-menth-2-en-1-ol (1.47), trans-p-menth-2-en-1-ol
62840
(0.50), and trans-dihydrocarvone (0.10) were obtained after 8 h when
50 μL mL−1 S-(−)-limonene was added (as a 20% solution in ethanol) in 50 mL of submerged
liquid culture inoculated with 0.5 mL of fresh spore suspension containing 9.9 × 107 spores
mL−1.
α-Pinene as substrate
Absidia corulea MTCC 1335 A. coruela in resting cell suspension was capable of biotransforming both (−)-α-pinene and
(+)-α-pinene with slight differences in the α-terpineol production, i.e., 34.12 mg and 28.15 mg
after 72 h for (+)- and (−)-α-pinene, respectively. Bioconversion also produced 9.53 and
9.77 mg of isoterpineol after 72 h with the substrates (+)- and (−)-α-pinene, respectively.
Aspergillus niger IOC-3913 Production of α-terpineol (~ 2.0 mg L−1), verbenone (~ 3.6), and verbenol (traces) after ~ 70 h
with immobilized cells (in a synthetic network). The biotransformation activity was not
growth-related.
Candida tropicalis MTCC
43 g or 77% of molar percentage yield of α-terpineol was reached after 96 h. Optimum condi230
tions: 100 mL reaction mix containing 0.5% (w/v) of α-pinene, incubated at 30 °C and shaking rotation.
Diaporthe sp. (teleomorph
form of Phomopsis)
Reference
Bier et al. (2017)
Maróstica and
Pastore (2007)
Bicas et al.
(2008a)
Adams et al.
(2003)
Tan and Day
(1998)
Tan et al. (1998)
Badee et al. (2011)
Tai et al. (2016)
Demyttenaere
et al. (2001)
Rottava et al.
(2011)
Demyttenaere
et al. (2001)
Siddhardha et al.
(2012)
Rozenbaum et al.
(2006)
Chatterjee et al.
(1999)
1268
Food Bioprocess Technol (2020) 13:1261–1279
Table 3 (continued)
Microorganism
Polyporus brumalis
β-Pinene as substrate
Aspergillus sp.
Aspergillus niger ATCC
9642
Aspergillus niger IOC-3913
Aspergillus niger ATCC
16404
Process details
Reference
This white rot fungus produced α-terpineol (24 mg L−1), fenchol (3.71 mg L−1) and borneol
(5.75 mg L−1) after 5 days when cultivated in SM medium (1% glucose, 0.02% ammonium
tartrate, 0.01% monopotassium phosphate, 0.05% magnesium sulfate, and 0.01% calcium
chloride) in shaken flasks at 26 °C and 80 rpm.
Lee et al. (2015)
Rottava et al.
Aspergillus sp. was isolated from leaves of citric fruit from the south of Brazil. Production of
(2011)
770 mg L−1 of α-terpineol was achieved when 2 g of biomass (inoculum) was cultivated for
168 h at 30 °C and 175 rpm in the presence of 1.75% substrate (as 1:1 ethanol mixture).
(−)β-pinene was added (as 1:1 ethanol mixture) in five steps (100 μL each 24 h). After
Toniazzo et al.
incubation at 25 °C, 150 rpm, and pH 6.0 for 72 h, the conversion achieved 4%.
(2005)
Production of ~ 160 mg L−1 after ~ 90 h with free cells. Production of ~ 80 mg mL−1 after up to Rozenbaum et al.
~ 160 h with immobilized cells. In both cases, the biotransformation activity was not
(2006)
growth-related.
Adding the substrate (1 mL.100 mL−1, in ethanol 1:1, v/v), 24 h after inoculation, into the culture Rottava et al.
(2010)
flasks with 30 mL of medium in orbital shaker (150 rpm) at 35 °C yielded a conversion in
α-terpineol of 15.5 g L−1 after 144 h.
different and complex structure. The de novo synthesis
strategy has been employed over the last few years for
the commercial biogeneration of different compounds for
the flavors and fragrances industry (Sales et al. 2018). In a
study on terpene biosynthesis, it was observed that αterpineol was one of the terpenes produced in greatest
abundance (up to 11 μg L−1) by all the Saccharomyces
cerevisiae wine yeasts tested (Carrau et al. 2005).
Recently, from the construction of a cell factory, αterpineol was produced by expressing the truncated αterpineol synthase (tVvTS) from Vitis vinifera in
S. cerevisiae (Zhang et al. 2019). The best terpineol production reached 1.88 mg L−1 using a 5-L bioreactor in
batch and fed-batch fermentation, offering a promising
means to substitute chemical synthesis or phytoextraction.
Properties
Chemical properties
Knowing the physicochemical properties of chemicals is essential for studies on biological properties and applications
(formulations). Table 4 summarizes the main properties of
α-terpineol and its enantiomers, where some minor deviations
are evidenced according to the different sources consulted.
Other properties, such as heat capacity, enthalpy, entropy,
and Gibbs energy of α-terpineol, have been calculated for a
wide temperature range of − 273.15–71.85 °C and may be
found in Markin et al. (Markin et al. 2016). Such information
is important for the thermodynamic analysis of processes and
thermodynamic databases, since it was still non-existent for αterpineol.
Biological Properties
The biological properties of a substance can be regarded as the
effects expressed on biological systems as a result of the interaction of the compound and the biological target. These
properties range from sensory perceptions to toxicity or therapeutic effects, as summarized in Table 5.
In terms of sensory effects, volatile compounds are perceptible when they exceed the odor detection threshold, which is
often as low as ng L−1 or ng kg−1, depending on the matrix in
which they are dispersed (Jeleń et al. 2012). α-Terpineol has
an odor detection threshold of 280–350 ppb and a taste threshold value of 2–25 ppm. When diluted in ethanol (1%), a pinelike, woody, and resinous aroma is evidenced, including a
slight cooling lemon and lime citrus nuance, and a floral dry
out. In addition to a woody, terpy, lemon and lemon–lime-like
taste characteristic, it also produces a slight soapy mouthfeel
(Burdock 2010). However, as commonly observed for other
biological properties, the sensory characteristics may vary depending on the enantiomer. In the case of α-terpineol, each of
its enantiomers (Fig. 1) has a particular aroma character: while
R-(+)-α-terpineol has a lilac (flower) odor, the S-(−)-enantiomer presents a coniferous, tarry, and cold pipe-like odor
(Boelens and van Gemert 1993).
As for the toxicological properties, there are no major concerns associated with α-terpineol. In 2011, a panel of experts
from the Flavor and Extract Manufacturers Association
(FEMA) initiated the safety reassessment of 2700 flavor ingredients so far labeled as “generally recognized as safe” (GRAS).
The study supported the conclusion that consumption of αterpineol as part of the food supply is not associated with any
significant risk to human health (Marnett et al. 2014).
Moreover, according to the Joint FAO/WHO Expert
Committee on Food Additives (JECFA), α-terpineol intake
Food Bioprocess Technol (2020) 13:1261–1279
Table 4
1269
Nomenclature, classifications, and physicochemical properties of α-terpineol
Names (synonyms)
α-Terpineol
3-Cyclohexene-1-methanol,α,α,4-trimethyl-; 1-p-menthen-8-ol; p-menth-1-en-8-ol; 2-(4-Methylcyclohex-3-en-1-yl)propan-2-ol;
1-Methyl-4-isopropyl-1-cyclohexen-8-ol; α-Terpilenol; Terpineol schlechthin
(+)-α-Terpineol (+)-(R)-α-Terpineol; d-α-Terpineol; 3-cyclohexene-1-methanol, α,α,4-trimethyl-, (R)-;
2-(4-Methylcyclohex-3-en-1-yl)propan-2-ol; (R)-α,α,4-Trimethylcyclohex-3-ene-1-methanol
(−)-α-Terpineol (S)-(−)-α-Terpineol; p-menth-1-en-8-ol (S); 3-myclohexene-1-methanol, α,α,4-trimethyl-, (S)-;
2-(4-Methylcyclohex-3-en-1-yl)propan-2-ol
Identifiers
CAS No.
EINECS No. CoE No.
FEMA No. FL No.
JECFA No.
α-Terpineol
98–55-5
202–680-6
62
3045
02.014
366
(+)-α-Terpineol 7785-53-7
232–081-5
(−)-α-Terpineol 10,482–56-1 233–986-8
Properties
Formula C10H18O
Molecular weight (Da) 154.25
Density 0.93 g mL−1 at 25 °C
XLogP3-AA 1.8
Melting point Flash point
Boiling Point Water solubility (25 °C) LogP (o/w) Optical rotation
Refract. index
α-Terpineol
35–41 °C
88.33 °C
217–219 °C 710 mg/L
2.67
– 103° to + 111.6° 1.474–1.486 at 20 °C
(+)-α-Terpineol 30–31 °C
90 °C
217.5 °C
371.7 mg/L
2.708
+ 21.1° to + 100.0° 1.482 at 20 °C
(−)-α-Terpineol 31–35 °C
90 °C
217–218 °C
371.7 mg/L
3.28
− 35.5° to − 110.3° 1.479–1.486 at 20 °C
Appearance
Colorless and viscous liquid.
Adapted from (Api et al. 2017; Bhatia et al. 2008; Burdock 2010; Li et al. 1998; Scifinder® 2019; The Good Scents Company Information System 2019)
represents “no safety concern at current levels of intake when
used as a flavoring agent” (JECFA 1998). A panel of experts
from the Research Institute of Fragrance Materials (RIFM)
conducted a toxicological and dermatological assessment of
cyclic and non-cyclic terpene alcohols used as fragrance ingredients. The panel defined, in an estimate with 10 categories of
cosmetic products, the volume of dermal systemic exposure,
the dose absorbed through the skin and available to systemic
circulation as 0.07 mg kg−1 day−1, with a maximum daily use
level of 5.7% of skin surface (Belsito et al. 2008).
The available information on acute toxicity for α-terpineol
is very comprehensive and based on oral, intraperitoneal, and
intramuscular studies (Bhatia et al. 2008). The LD50 determined in male mice (oral) was 2.9 g kg−1 with a 95% confidence interval (CI) of 2.3–3.3 g kg−1 (Yamahara et al. 1985).
In intraperitoneal administration, the combined LD50 in males
and females was calculated to be 0.847 g kg−1 with a 95% CI
0.70–1.01 g kg−1 (RIFM 1984). The LD50 was calculated to
be 2 g kg−1 in an intramuscular study with mice (Northover
and Verghese 1962). In a more recent revision of the human
health safety assessment of the RIFM Expert Panel for
Fragrance Safety (Api et al. 2017), α-terpineol was defined
as non-genotoxic, non-skin sensitizing, and non-phototoxic/
photoallergenic. In relation to NOAEL (no observed adverse
effect level), the values established were for repeated dose
toxicity 578 mg kg−1 day−1; for developmental toxicity
200 mg kg − 1 day − 1 ; and for reproductive toxicity
250 mg kg−1 day−1. This leads to the conclusion that αterpineol is safe for use as a fragrance under the limits
described in the safety assessment of the RIFM Criteria
Document (Api et al. 2015).
On the other hand, a mouse study in which α-terpineol was
orally administered for 2 weeks (100 and 500 mg kgbw−1 day−1)
showed that α-terpineol induced hepatic lipid accumulation
(Choi et al. 2013), indicating possible side effects of αterpineol consumption in such doses. In a scientific opinion
requested by the European Commission, α-terpineol was considered safe for all animal species when used as feed at the
high use level of 5 mg kg−1 complete feed with a margin of
safety of 1.2–12 mg kg−1. However, the report warned that the
use of feed flavorings has the potential of altering the organoleptic quality of animal products (e.g., milk, eggs). Finally,
the same report also considered α-terpineol safe for the environment based on its abundance in plant materials present in
European countries and safe to the soil compartment when
used in animal feeds at safe levels (FEEDAP 2012).
In the last few years, α-terpineol has also been increasingly
associated with other biological effects, such as anti-inflammatory, antioxidant, antiproliferative, and antimicrobial activities (Khaleel et al. 2018). In terms of anti-inflammatory activity, α-terpineol has been shown to suppress the formation
of IL-6 in epithelial buccal cells (Held et al. 2007). It also
showed anti-inflammatory activity, significantly reducing the
production of interleukins (IL-10, anti-inflammatory; IL-6 and
IL-1β, pro-inflammatory) in human macrophages (Nogueira
et al. 2014). The reduction of serum levels of proinflammatory cytokines IL-1β and TNF-α was also evidenced in obesity animal models, suggesting that both R-(+
1270
Table 5
Food Bioprocess Technol (2020) 13:1261–1279
Biological properties of α-terpineol
Biological
property
Sensory
Toxicological
Comments
Reference
Odor detection threshold of 280–350 ppb and a taste threshold value of 2–25 ppm.
Jeleń et al. (2012)
R-(+)-α-terpineol: a lilac (flower) odor; S-(−)-α-terpineol: coniferous, tarry and cold pipe-like odor.
Boelens and van Gemert
(1993)
Marnett et al. (2014)
Not associated with any significant risk to human health.
No safety concern at current levels of intake when used as a flavoring agent.
Volume of dermal systemic exposure: 0.07 mg kg−1 day−1; maximum daily use level 5.7% of skin
surface.
LD50 2.9 g kg−1 in male mice (oral). Confidence interval 95% of 2.3–3.3 g kg−1.
−1
LD50 0.847 g kg in male and female mice (intraperitoneal). Confidence interval 95% of
0.70–1.01 g kg−1.
LD50 2.0 g kg−1 in mice (intramuscular).
Non-genotoxic, non-skin sensitizing, and non-phototoxic/photoallergenic.
Therapeutic
NOAEL (mg kg−1 day−1): Repeated dose toxicity 578; developmental toxicity 200; reproductive
toxicity 250.
Safe for all animal species (margin of safety of 1.2–12 mg kg−1) and safe for the environment.
Anti-inflammatory activity, suppressing the formation of IL-6 in epithelial buccal cells.
JECFA (1998)
Belsito et al. (2008)
Yamahara et al. (1985)
RIFM (1984)
Northover and Verghese
(1962)
Api et al. (2017)
Api et al. (2015)
FEEDAP (2012)
Held et al. (2007)
Anti-inflammatory activity, significantly reducing the production of interleukins in human macrophage. Nogueira et al. (2014)
Anti-inflammatory activity, reducing the serum levels of pro-inflammatory cytokines IL-1β and TNF-α Sousa et al. in press
in rats.
Treatment of allergic inflammation and asthma in male Swiss mice.
Pina et al. (2019)
Antioxidant activity: DPPH, TBA, superoxide anion release, and glutathione S-transferase activity.
Maróstica Jr. et al. (2009)
Antioxidant activity (ORAC) and in vitro antiproliferative activity against breast carcinoma and chronic Bicas et al. (2011)
myeloid leukemia.
Antiproliferative activity against non-small cell lung carcinoma.
Hassan et al. (2010)
Stronger viability reduction in tumor cell lines and stronger apoptosis induction in HeLa.
Zhang et al. (2018)
Antiproliferative activity in vitro on melanoma cell lines.
Batista et al. (2019)
Antimutagenic activity in Ames’ test and indirect antioxidant activity.
Di Sotto et al. (2013)
Antidiarrheal activity in models of acute diarrhea in Swiss mice.
dos Santos Negreiros et al.
(2019)
Increase of growth performance and alleviation of intestinal damage in piglets challenged with E. coli. Yi et al. (2018)
Antimicrobial
Anticonvulsant activity in male Swiss mice.
Sousa et al., (2007a)
Sedative activity in male Swiss mice.
Sousa et al., (2007b)
Analgesic activity in mice.
Quintans-Júnior et al.
(2011)
Reduction of cancer pain in Swiss mice.
Gouveia et al. (2018)
Cytostatic and cytocidal effects towards Geotrichum citri-aurantii.
Zhou et al. (2014)
Effectively inhibit mycelium growth and spore germination of A. niger.
An et al. (2019)
Antimycotic and antimycotoxigenic effects.
Chaudhari et al. (2020)
Activity against Staphylococcus epidermidis ATCC 1222.
Dasgupta et al. (2019)
)- and S-(−)-α-terpineol could, at least in part, counteract the
effect of a high-fat diet in Sprague-Dawley rats (Sousa et al. in
press). A recent study indicates that alcoholic monoterpenes
(citronellol, α-terpineol, and carvacrol) may be an alternative
for the treatment of allergic inflammation and asthma. The
administration of monoterpenes (25, 50, or 100 mg kg−1,
i.p.) to male Swiss mice 1 h prior to ovalbumin (OVA)-
induced asthma significantly decreased leukocyte migration
and TNF-α levels, possibly by modulating COX, PGE2, and
H1 receptors (Pina et al. 2019). Furthermore, new α-terpineol
derivatives could be produced (by condensation with different
anhydrides or acyl chlorides; condensation with bromoacetyl
bromide, followed by nucleophilic substitution at the αposition of the ester carbonyl functionality of the intermediate
Food Bioprocess Technol (2020) 13:1261–1279
compound; and catalytic hydrogenation) in order to pursue
more favorable biological properties, such as improved bioavailability and prolonged elimination half-life. Of these,
eight derivatives showed enhanced airway smooth muscle relaxation activity (Zhu et al. 2018).
The antioxidant capacity of α-terpineol has also been reported in the last few years. One of the first studies on this
subject evaluated the antioxidant potential of R-(+)-limonene
biotransformation products based on the 2,2-diphenyl-1picrylhydrazyl (DPPH) radical-scavenging assay, lipid peroxidation by the thiobarbituric acid (TBA) assay, superoxide
anion release by cultured leukemic cells, and glutathione Stransferase (GSTs) activity. The authors concluded that αterpineol showed important antioxidant activity (Maróstica
Jr et al. 2009). Some years later, the oxygen radical absorbance capacity (ORAC) assay was also used to evaluate the
antioxidant capacity of α-terpineol, whose result (ORAC value of 2.72 μmol Trolox equiv./μmol) was comparable with
the synthetic antioxidant BHA (Bicas et al. 2011). The same
study also evaluated the in vitro antiproliferative effect of αterpineol against nine tumor cells. The most encouraging results were found for breast carcinoma and chronic myeloid
leukemia, for which the cytostatic effect of α-terpineol was
evidenced at concentrations of 181 μM and 249 μM, respectively (Bicas et al. 2011).
The antiproliferative activity of α-terpineol has also been
demonstrated for other cancer cell lines, particularly nonsmall cell lung carcinoma, for which IC50 was 260 μM. This
study showed that α-terpineol acted by reducing the expression of nuclear transcription factor NF-κB (Hassan et al.
2010). In another report, α-terpineol was not itself responsible
for the antiproliferative effect, but was able to interfere with
the production of Antrodia cinnamomea triterpenoids (ACT)
associated with this biological activity. The addition of
0.05 mL L−1 of α-terpineol—as an elicitor to increase the
production of ACT in mycelia in solid-state culture—
changed the content, the compound profile, and the bioactivity
of ACT, i.e., it resulted in stronger viability reduction in several tumor cell lines and stronger apoptosis induction in HeLa
cell line in a dose-dependent manner (Zhang et al. 2018). The
in vitro antiproliferative effect of α-terpineol on melanoma
cell lines was also assessed using a drug delivery system
(DDS) miniemulsion consisting of α-terpineol-loaded
(400 mg) nanoparticles immobilized in a poly(methyl methacrylate) (PMMA) matrix. A dose-dependent cytotoxic effect
was identified against human (SK-MEL-28) and murine
(B16-F10) melanoma cell lines while no significant toxic effects were observed for normal cell lines, such as human macrophages and fibroblasts (MRC-5) (Batista et al. 2019).
The antimutagenic effect of α-terpineol in Ames’ test and
the indirect antioxidant effect (Fe2+-chelating activity) of αterpineol were also reported (Di Sotto et al. 2013). Recently,
the antioxidant activity of α-terpineol was demonstrated
1271
in vivo, in the abovementioned obesity model study. The serum and liver thiobarbituric acid reactive substances
(TBARS) levels were significantly lower when a high-fat diet
was supplemented with R-(+)- or S-(−)-α-terpineol (Sousa
et al., in press).
In another rodent study, α-terpineol presented high antidiarrheal potential in models of acute diarrhea in Swiss mice
(castor oil-induced diarrhea), inflammatory diarrhea (induction by prostaglandin E2), and secretory diarrhea (cholera
toxin-induced model), resulting from the ability of this monoterpene alcohol to inhibit intestinal motility by means of anticholinergic mechanisms and, consequently, to prevent the accumulation of intestinal fluid and to reduce the secretion of
water and chlorides to the intestinal lumen (dos Santos
Negreiros et al. 2019). In the same study, it was observed that
α-terpineol also reduced fluid formation and loss of Cl− ions
by interacting directly with GM1 receptors and cholera toxin,
thus increasing the uptake of intestinal fluids. When administered to piglets as dietary supplementation at 100 mg kg−1 feed
(Yi et al. 2018), α-terpineol was able to increase growth performance and to alleviate intestinal damage in piglets challenged with Escherichia coli. In addition, α-terpineol supplementation increased the ADFI (average daily feed intake) and
ADG (average daily weight gain) in E. coli-challenged piglets
by 18% and 19%, respectively, in comparison with the control
group.
α-Terpineol also showed promising results as an anticonvulsant agent in male Swiss mice by increasing the latency to
convulsions induced by pentylenetetrazole at doses of 100 and
200 mg kg−1 and by decreasing the incidence of hindlimb
extension produced by electroconvulsive shock in a doserelated manner at doses of 200 and 400 mg kgbw−1 (Sousa
et al. 2007a). The same research group evaluated 10 monoterpenes in mice and found that α-terpineol showed a depressant
effect in the pentobarbital-induced sleep test, suggesting a
sedative effect of this compound (Sousa et al. 2007b).
Analgesic action has also been demonstrated for α-terpineol. The administration of α-terpineol (25, 50, and 100 mg kg
bw−1, i.p.) in mice presented analgesia activity with no apparent interference with motor ability using the acetic acid writhing reflex, formalin, glutamate, and capsaicin-induced
nociception tests (Quintans-Júnior et al. 2011). The role of
the L-arginine/SNAP/NO/cGMP/KATP channel pathway in
analgesic effects of α-terpineol was then studied. The
antinociceptive effect was significantly potentiated by L-arginine, while significantly antagonized by L-NAME.
Glibenclamide significantly reversed the α-terpineol-induced
antinociception, indicating the involvement of KATP channels
in the antinociceptive effect of α-terpineol. The authors concluded that the antinociceptive effect of α-terpineol is mediated through a channel pathway (Safaripour et al. 2018). αTerpineol also reduces cancer pain in Swiss mice by increasing antioxidant capacity and defense, with no evident
1272
biochemical and hematological toxicity observed (Gouveia
et al. 2018).
The antimicrobial activity of α-terpineol has been known
for a long time (Penfold and Grant 1925). In recent years,
attention has been given to the antimycotic effect of this
monoterpene alcohol as a strategy to overcome fungal contamination, to control post-harvest deterioration and to avoid
mycotoxin production in agricultural products. For instance,
α-terpineol presented cytostatic (MIC) and cytocidal effects
(MFC) towards Geotrichum citri-aurantii, one of the most
important citrus pathogens, at concentrations of 2.00 mL/mL
and 4.00 mL/mL (Zhou et al. 2014). Moreover, among the
compounds tested in a study, namely, tea tree oil and its main
components, terpinen-4-ol (34.95%, mol/mol), 3-carene
(14.48%), and α-terpineol (12.04%), this last was the most
significant in increasing cytoplasmatic membrane permeability, in interfering with microscopic morphology of hyphae and
spores, and in impairing key metabolic routes of Aspergillus
niger. As a result, this monoterpenoid was able to effectively
inhibit mycelium growth and spore germination of A. niger,
decreasing both the incidence of black mold disease and lesion
diameter in harvested grapes (An et al. 2019). Finally, αterpineol encapsulation in an α-terpineol-loaded chitosan
nanoemulsion was described as a strategy to enhance its effect
on the reduction of fungal contamination, incidence of aflatoxin B,1 and free radical deterioration of stored maize, without interfering with the product’s sensory attributes. The
mechanistic investigation suggested that the antimycotic and
antimycotoxigenic effects, in this case, were caused by
inhibiting ergosterol biosynthesis, increasing the leakage and
loss of cellular ions and 260 and 280 nm absorbing materials,
and by inhibiting methylglyoxal (Chaudhari et al. 2020). The
antibacterial effect of a mixture of α-terpineol, thymol, and a
cationic phospholipid complex was also considered for the
development of a leave-on skin care product presenting activity against Staphylococcus epidermidis ATCC 1222
(Dasgupta et al. 2019).
Current Market and Applications
α-Terpineol is widely used in the industry, mainly as aroma in
food (beverages, confectionery, frozen foodstuff, and condiments) and as fragrance in cosmetics and toiletries (perfumes,
fine fragrances, body lotions, soaps, shaving products, oral care,
wipes, and nail polish remover) (www.mintel.com/global-newproducts-database). Indeed, its major use is as a starting
compound for formulating fragrances, with a world production
between 100 and 1000 tons (Belsito et al. 2008). It is a key
component in lime flavorings (Margetts 2004)—although limonene is the most abundant volatile in citrus—the combination of
α-terpineol and citral yields the flavor character of lime
(McGorrin 2002). A mixture of isomers (mainly α- but also a
Food Bioprocess Technol (2020) 13:1261–1279
considerable amount of γ-terpineol) composes the most important commercial grade terpineol, which is stronger in lilac odor
than the pure crystalline α-terpineol (Surburg and Panten 2016).
The aromas and fragrances global market, in which αterpineol is included, reached US$ 28.2 billion in 2017, an
increase of 4.6% compared with 2016, and is expected to
grow at an average annual rate of 4.9% per annum to reach
approximately US$ 36 billion in 2022 (IAL Consultants
2018). The price of α-terpineol depends on the purpose of
application of the compound: regarding technical grade αterpineol, the price ranges from US$ 0.60 to 0.90 per g, while
for analytical standard and primary reference standard, the
prices are in the range of US$ 300.00–590.00 per g and US$
2300.00 per g, respectively (www.sigmaaldrich.com). In
general, as a fragrance ingredient, α-terpineol is marketed at
US$ 70.00 per kg. This value is lower in comparison with the
prices of other aroma compounds widely used by the industry,
such as vanillin (US$ 170), linalool (US$ 180), and citronellol
(US$ 200), for example (www.perfumersworld.com). The
individual consumption of this alcohol has been estimated as
17.23 μg kg−1 day−1 (Burdock 2010).
The Code of Federal Regulations Title 21 of FDA
(21CFR172.515, US Food and Drug Administration), last revised in 2018, establishes α-terpineol as “food additives permitted for direct addition to food for human consumption,”
provided it is used in the minimum quantity required to produce its intended effect, and otherwise in accordance with all
the principles of good manufacturing practice (US FDA
2018). FDA also authorizes the use of up to 11% αterpineol in topical lotion as an inactive ingredient, i.e., a component of a drug product other than the active ingredient (US
FDA / CDER, www.accessdata.fda.gov/scripts/cder/iig/
index.Cfm). The reported uses of α-terpineol according to
FEMA for each foodstuff (usual level; maximal level, in
ppm) are the following: beverages (0.58; 2.12), baked goods
(15.93; 19.52), chewing gum (13.53; 83.47), condiments and
relishes (25.91; 44.55), frozen dairy (9.23; 14.00), gelatins
and puddings (8.56; 12.64), gravies (3.00; 6.00), hard candy
(10.67; 17.39), meat products (5.27; 10.54), nonalcoholic beverages (3.40; 5.41), and soft candy (13.51; 16.50) (Burdock
2010). The Council of Europe (CoE), by means of Regulation
(EU) No. 872/2012, lists α-terpineol as a flavoring substance
for use in food (maximum of 40 ppm).
The olfactory characteristics of α-terpineol are also desired
in other product categories, such as scented candles, tobacco,
household (air fresheners, bathroom, dishwashing, floor,
kitchen and window cleaning), soap, and detergents (fabric
detergents, fabric softeners, washing powders, and washing
soaps) (https://householdproducts.nlm.nih.gov/; www.
mintel.com/global-new-products-database). Other more
distinct products also apply α-terpineol in their formulations,
such as insecticides and anti-mites (www.mintel.com/globalnew-products-database).
Food Bioprocess Technol (2020) 13:1261–1279
In the pharmaceutical industry, α-terpineol is marketed in
combination with other terpenes (such as camphor,
chlorothymol, eucalyptol, menthol) in capsules for treatment
of blockage in nasal passages, common cold, cough, cold
sores, colds, airway mucus hypersecretion, asthma, pain in
muscle strains or sprains, back pain, itching, and other conditions (https://www.pharmacompass.com/activepharmaceutical-ingredients/alpha-terpineol). α-Terpineol is
also applied in aromatherapy formulations. This monoterpene
was present, for instance, in the five most important components of pine oil (20.50%, second most abundant) and lime oil
(7.6%, third most abundant) used in aromatherapy (Tadtong
et al. 2015).
In addition to these traditional uses of α-terpineol, other
studies show that this compound might have other potential
applications. An invention reported that α-terpineol may be
used as an additive (12–14%) to decrease the flammability of
normally flammable alcohols and solvents (acetone, methanol, ethyl acetate, ethanol, and xylene, to name a few), increasing the flash points by 50–60 °C. The resulting mixture can
then be blended with other organic solvents to produce performance solvents, such as paint strippers with flash points
greater than 60 °C to meet regulation specifications (Koetzle
2004). Several studies have reported the use of α-terpineol as
a suspending solvent in the process of manufacturing solid
oxide fuel cells (SOFCs) (He et al. 2010; Yoon et al. 2007a;
Yoon et al. 2007b). As a bio-derivative product and with a
calorific value higher than that of ethanol, terpineol (with predominance of the α-terpineol isomer) was used as an octane
booster for gasoline in a spark-ignited engine. The test with
terpineol-blended non-oxygenated gasoline enabled spark
timing advancement and improved engine combustion.
Increasing proportions of terpineol in the blend improved
peak heat release rate, in-cylinder pressure, CA50 (crank angle position in which 50% of the heat is released), and combustion duration to values similar to those of commercial
European gasoline. Non-oxygenated gasoline supplemented
with 30% terpineol showed improved combustion characteristics when compared with commercial European gasoline
(Vallinayagam et al. 2017).
Another use of α-terpineol is as an insect attractant. In a
recent study (Mitchell et al. 2018), it was reported that the
mixture of the pheromone of Megacyllene antennata, a species native to southwestern North America whose larvae feed
on woody tissues of mesquite, is composed mainly of (S)-αterpineol and (E)-2-hexenol, and that the synthetically reconstructed mixture attracted males and females of M. antennata
during field bioassays. As a strategy to attract female
Mediterranean sand flies (Phlebotomus papatasi) to an insect
trap, α-terpineol (1% and 45%) was used in a mixture with
polymer as an insect attractant (Wilson et al. 1989). Similarly,
the insect attractant property of monoterpenes was used as
biological pest control strategy: a mixture of (E)-2-hexenal,
1273
α-terpineol, linalool, terpinen-4-ol, and benzyl alcohol was
able to effectively attract adult spined soldier bugs (Podisus
maculiventris), which then preyed gypsy moth caterpillars and
larvae of beetles, such as the Colorado potato beetle and the
Mexican bean beetle (Aldrich et al. 2015).
α-Terpineol may also be applied for its antimicrobial activity. This monoterpene alcohol presented antifungal activity
and inhibited the rot caused by Aspergillus niger (An et al.
2019) and Aspergillus ochraceus (Kong et al. 2019) in postharvest grapes, suggesting its possible use as a food preservative. Similarly, an algaecide effect has also been attributed to
α-terpineol. When tested against Chlamydomonas reinhardtii
(Chen et al. 2019), this compound increased 1.3-fold the H2O2
content burst in the target microalga after 1 h. The authors
suggested that its killing mechanism was triggering programmed cell death by causing reactive oxygen species
increase.
Concluding Remarks
This paper presented the increasing number of reports on nonobvious biological activities assigned to α-terpineol (other
than its sensory attributes) in the last 10–15 years. The evolution of this science field, giving rise to stronger evidence of
these properties, will likely increase the investigation of health
applications of α-terpineol. It is widely accepted, for instance,
that antioxidant and anti-inflammatory compounds present in
foods may help prevent and reduce the effects of major health
problems, such as obesity, cardiovascular diseases, and neurodegenerative disorders (Prasad et al. 2015; Ribeiro et al.
2019; Teodoro 2019; Zhang et al. 2015). Thus, in the context
of functional foods or nutraceuticals, α-terpineol-containing
food products may emerge as an auxiliary tool to counteract
some medical conditions. Similarly, the pharmaceutical industry can benefit from some of those α-terpineol properties (e.g.,
anti-inflammatory, antiproliferative, and antinociceptive activities) in the formulation of new drugs or illness treating
protocols. To illustrate this possibility, perillyl alcohol, a
monocyclic monoterpene alcohol structurally related to α-terpineol, has already been used in clinical trials to treat glioma
cancers (Chen et al. 2018). In this scenario, there would be a
demand for α-terpineol, impacting on its market.
Currently, α-terpineol is an abundant and low-priced compound, but the commercially available products are not
enantiomerically pure (Ravid et al. 1995; Sousa et al., in
press). However, when it comes to biological properties, chiral analyses are usually indicated in order to maximize clinical
effects or mitigate drug toxicity (Smith 2009). For this reason,
the discovery of different biological properties associated with
each enantiomer may increase the specific demand for
enantiomerically enriched compounds. Therefore, new αterpineol sources may become necessary. This review shows
1274
that one of such promising “sources” to meet this demand
would be biotechnological production processes using microorganisms to biotransform inexpensive and widely available
monoterpene substrates, such as limonene and α- or β-pinenes. Some of these bioprocesses—which can yield αterpineol on a scale of hundreds of grams per liter—have
already been reported and indicate the potential to use this
monoterpene alcohol of natural origin (fermentation) in applications that transcend the flavors and fragrances industry.
Acknowledgments The authors thank Espaço da Escrita –
Coordenadoria Geral da Universidade (UNICAMP) for the language services provided.
Funding Information Adones Sales received grant from Instituto
Euvaldo Lodi (IEL/PR) and CNPq (grant number 350020/2018-3) and
CAPES (process number 23038.000795/2018-61). This study was
funded by the National Council of Technological and Scientific
Development (CNPq) (grant number 400411/2016-4); the São Paulo
Research Foundation (FAPESP) (grant number 2016/21619-7); and the
Coordination for the Improvement of Higher Education Personnel
(CAPES) (process number 23038.000795/2018-61, Finance Code 001).
Moreover, Lorena de Oliveira Felipe is grateful to the Ministry of
Education, Culture, Sports, Science and Technology (MEXT Monbukagakusho) for the Doctoral Grant (recipient no. 177307) provided by the Japanese Government.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflict of
interest.
References
Abraham, W. R., Hoffmann, H. M. R., Kieslich, K., Reng, G., & Stumpf,
B. (1985). Microbial transformations of some monoterpenoids and
sesquiterpenoids (pp. 146–170). Ciba Found: Enzymes in Organic
Synthesis. https://doi.org/10.1002/9780470720929.ch11.
Adams, A., Demyttenaere, J. C. R., & Kimpe, N. D. (2003).
Biotransformation of (R)-(+)- and (S)-(−)-limonene to alphaterpineol by Penicillium digitatum—investigation of the culture
conditions. Food Chemistry, 80(4), 525–534.
Aldrich, J. R., Kochansky, J. P., & Abrams, C. B. (2015). Attractant for a
beneficial insect and its parasitoids: pheromone of the predatory
spined soldier bug, Podisus maculiventris (Hemiptera:
Pentatomidae) 1. Environmental Entomology, 13(4), 1031–1036.
https://doi.org/10.1093/ee/13.4.1031.
Alfaro, M., Oguiza, J. A. A., Ramírez, L., & Pisabarro, A. G. G. (2014).
Comparative analysis of secretomes in basidiomycete fungi. Journal
of Proteomics, 102, 28–43. https://doi.org/10.1016/j.jprot.2014.03.
001.
Alves, M. F., Blank, A. F., Andrade, T. M., Nizio, D. A. C., Sampaio, T.
S., & de Nascimento Junior, A. F. (2018). Content and chemical
composition of the essential oil of myrcia lundiana kiaersk in different drying times. Bioscience Journal, 34(3), 623–628. https://doi.
org/10.14393/BJ-v34n3a2018-39371.
An, P., Yang, X., Yu, J., Qi, J., Ren, X., & Kong, Q. (2019). α-Terpineol
and terpene-4-ol, the critical components of tea tree oil, exert antifungal activities in vitro and in vivo against Aspergillus niger in
grapes by inducing morphous damage and metabolic changes of
Food Bioprocess Technol (2020) 13:1261–1279
fungus. Food Control, 98, 42–53. https://doi.org/10.1016/j.
foodcont.2018.11.013.
Api, A. M., Belsito, D., Bruze, M., Cadby, P., Calow, P., Dagli, M. L.,
Dekant, W., Ellis, G., Fryer, A. D., Fukayama, M., Griem, P.,
Hickey, C., Kromidas, L., Lalko, J. F., Liebler, D. C., Miyachi, Y.,
Politano, V. T., Renskers, K., Ritacco, G., Salvito, D., Schultz, T.
W., Sipes, I. G., Smith, B., Vitale, D., & Wilcox, D. K. (2015).
Criteria for the Research Institute for Fragrance Materials, Inc.
(RIFM) safety evaluation process for fragrance ingredients. Food
and Chemical Toxicology, 82(S), S1–S19. https://doi.org/10.1016/
j.fct.2014.11.014.
Api, A. M., Belsito, D., Bhatia, S., Botelho, D., Browne, D., Bruze, M.,
Burton Jr., A., Buschmann, J., Calow, P., Dagli, M. L., Date, M.,
Dekant, W., Deodhar, C., Fryer, A. D., Joshi, K., Kromidas, L., la
Cava, S., Lalko, J. F., Lapczynski, A., Liebler, D. C., Miyachi, Y.,
O’Brien, D., Parakhia, R., Patel, A., Penning, T. M., Politano, V. T.,
Ritacco, G., Romine, J., Salvito, D., Schultz, T. W., Shen, J., Sipes,
I. G., Thakkar, Y., Tokura, Y., Tsang, S., Wahler, J., Wall, B., &
Wilcox, D. K. (2017). RIFM fragrance ingredient safety assessment,
terpineol, CAS registry number 8000-41-7. Food and Chemical
Toxicology, 110, S392–S402. https://doi.org/10.1016/j.fct.2017.07.
042.
Atti-Santos, A. C., Rossato, M., Serafini, L. A., Cassel, E., & Moyna, P.
(2005). Extraction of essential oils from lime (Citrus latifolia tanaka)
by hydrodistillation and supercritical carbon dioxide. Brazilian
Archives of Biology and Technology, 48(1), 155–160. https://doi.
org/10.1590/S1516-89132005000100020.
Badee, A. Z. M., Helmy, S. A., & Morsy, N. F. S. (2011). Utilisation of
orange peel in the production of α-terpineol by Penicillium
digitatum (NRRL 1202). Food Chemistry, 126(3), 849–854.
https://doi.org/10.1016/j.foodchem.2010.11.046.
Baser, K. H. C., Kirimer, N., & Tümen, G. (1993). Composition of the
essential oil of Origanum majorana L From Turkey. Journal of
Essential Oil Research, 5(5), 577–579. https://doi.org/10.1080/
10412905.1993.9698283.
Batista, F. A., Fontele, S. B. C., Santos, L. K. B., Filgueiras, L. A.,
Nascimento, S. Q.,de e Sousa, J. M. C., et al. (2019). Synthesis,
characterization of α-terpineol-loaded PMMA nanoparticles as proposed of therapy for melanoma. Materials Today Communications,
100762.
Belsito, D., Bickers, D., Bruze, M., Calow, P., Greim, H., Hanifin, J. M.
M., et al. (2008). A toxicologic and dermatologic assessment of
cyclic and non-cyclic terpene alcohols when used as fragrance ingredients. Food and Chemical Toxicology, 46(11 SUPPL). https://
doi.org/10.1016/j.fct.2008.06.085.
Bhatia, S. P., Letizia, C. S., & Api, A. M. (2008). Fragrance material
review on alpha-terpineol. Food and Chemical Toxicology, 46,
S280–S285.
Bicas, J. L., Barros, F. F. C., Wagner, R., Godoy, H. T., & Pastore, G. M.
(2008a). Optimization of R-(+)-α-terpineol production by the biotransformation of R-(+)-limonene. Journal of Industrial
Microbiology and Biotechnology, 35(9), 1061–1070. https://doi.
org/10.1007/s10295-008-0383-0.
Bicas, J. L., Fontanille, P., Pastore, G. M., & Larroche, C. (2008b).
Characterization of monoterpene biotransformation in two pseudomonads. Journal of Applied Microbiology, 105(6), 1991–2001.
https://doi.org/10.1111/j.1365-2672.2008.03923.x.
Bicas, J. L., Fontanille, P., Pastore, G. M., & Larroche, C. (2010). A
bioprocess for the production of high concentrations of R-(+)-alpha-terpineol from R-(+)-limonene. Process Biochemistry, 45(4),
481–486. https://doi.org/10.1016/j.procbio.2009.11.007.
Bicas, J. L., Neri-Numa, I. A., Ruiz, A. L. T. G., De Carvalho, J. E., &
Pastore, G. M. (2011). Evaluation of the antioxidant and antiproliferative potential of bioflavors. Food and Chemical Toxicology,
49(7), 1610–1615. https://doi.org/10.1016/j.fct.2011.04.012.
Food Bioprocess Technol (2020) 13:1261–1279
Bier, M. C. J., Medeiros, A. B. P., & Soccol, C. R. (2017).
Biotransformation of limonene by an endophytic fungus using synthetic and orange residue-based media. Fungal Biology, 121(2),
137–144. https://doi.org/10.1016/j.funbio.2016.11.003.
Boelens, M. H., & van Gemert, L. (1993). Sensory properties of optical
isomers. Perfurmer Flavorist, 18, 1–16. https://doi.org/10.1017/
CBO9781107415324.004.
Boussaada, O., & Chemli, R. (2006). Chemical composition of essential
oils from flowers, leaves and peel of citrus aurantium l. var. amara
from Tunisia. Journal of Essential Oil-Bearing Plants, 9(2), 133–
139. https://doi.org/10.1080/0972060X.2006.10643484.
Boussaada, O., & Chemli, R. (2007). Seasonal variation of essential oil
composition of Citrus Aurantium L. var. amara. Journal of Essential
Oil-Bearing Plants, 10(2), 109–120. https://doi.org/10.1080/
0972060X.2007.10643528.
Brazilian Ministry of Industry Foreign Trade and Services, M. (2019).
Export and Import General. Available at: http://comexstat.mdic.gov.
br/pt/geral
Burdock, G. A. (2010). Fenaroli’s handbook of flavor ingredients (6th
ed.). Boca Raton: CRC Press. https://doi.org/10.1016/S00156264(76)80260-X.
Cadwallader, K. R., Braddock, R. J., Parish, M. E., Higgins, D. P.,
Cadwallader, K. R., Braddock, R. J., Parish, M. E., & Higins, D.
P. (1989). Bioconversion of (+)-limonene by Pseudomonas gladioli.
Jornal of Food Science, 54(5), 1241–1245. https://doi.org/10.1111/
j.1365-2621.1989.tb05964.x.
Carrau, F. M., Medina, K., Boido, E., Farina, L., Gaggero, C., Dellacassa,
E., Versini, G., & Henschke, P. A. (2005). De novo synthesis of
monoterpenes by Saccharomyces cerevisiae wine yeasts. FEMS
Microbiology Letters, 243(1), 107–115. https://doi.org/10.1016/j.
femsle.2004.11.050.
Carroll, J. F., Tabanca, N., Kramer, M., Elejalde, N. M., Wedge, D. E.,
Bernier, U. R., Coy, M., Becnel, J. J., Demirci, B., Başer, K. H. C.,
Zhang, J., & Zhang, S. (2011). Essential oils of Cupressus funebris,
Juniperus communis, and J. chinensis (Cupressaceae) as repellents
against ticks (Acari: Ixodidae) and mosquitoes (Diptera: Culicidae)
and as toxicants against mosquitoes. Journal of Vector Ecology,
36(2), 258–268. https://doi.org/10.1111/j.1948-7134.2011.00166.x.
Chandran, J., Amma, K. P. P., Menon, N., Purushothaman, J., & Nisha, P.
(2012). Effect of enzyme assisted extraction on quality and yield of
volatile oil from black pepper and cardamom. Food Science and
Biotechnology, 21(6), 1611–1617. https://doi.org/10.1007/s10068012-0214-y.
Chatterjee, T., De, B. K., & Bhattacharyya, D. K. (1999). Microbial
oxidation of alpha-pinene to (+)-alpha-terpineol by Candida
tropicalis. Indian Journal of Chemistry, 38(40), 515–517. https://
doi.org/10.1002/chin.199940164.
Chaudhari, A. K., Singh, A., Kumar Singh, V., Kumar Dwivedy, A., Das,
S., Grace Ramsdam, M., et al. (2020). Assessment of chitosan biopolymer encapsulated α-Terpineol against fungal, aflatoxin B1
(AFB1) and free radicals mediated deterioration of stored maize
and possible mode of action. Food Chemistry, 311. https://doi.org/
10.1016/j.foodchem.2019.126010.
Chen, T. C., da Fonseca, C. O., & Schönthal, A. H. (2018). Intranasal
perillyl alcohol for glioma therapy: molecular mechanisms and clinical development. International Journal of Molecular Sciences,
19(12). https://doi.org/10.3390/ijms19123905.
Chen, Y., Weng, Y., Zhou, M., Meng, Y., Liu, J., Yang, L., & Zuo, Z.
(2019). Linalool- and α-terpineol-induced programmed cell death in
Chlamydomonas reinhardtii. Ecotoxicology and Environmental
Safety, 167, 435–440. https://doi.org/10.1016/j.ecoenv.2018.10.
062.
Chisholm, M. G., Wilson, M. A., & Gaskey, G. M. (2003).
Characterization of aroma volatiles in key lime essential oils
(Citrus aurantifolia Swingle). Flavour and Fragrance Journal,
18(2), 106–115. https://doi.org/10.1002/ffj.1172.
1275
Choi, Y. J., Sim, W. C., Choi, H. K., Lee, S. H., & Lee, B. H. (2013). αTerpineol induces fatty liver in mice mediated by the AMP-activated
kinase and sterol response element binding protein pathway. Food
and Chemical Toxicology, 55, 129–136. https://doi.org/10.1016/j.
fct.2012.12.025.
Cleff, M. B., Meinerz, A. R., Xavier, M., Schuch, L. F., Meireles, M. C.
A., Rodrigues, M. R. A., & de Mello, J. R. B. (2010). In vitro
activity of Origanum vulgare essential oil against Candida species.
Brazilian Journal of Microbiology, 41(1), 116–123. https://doi.org/
10.1590/S1517-83822010000100018.
Consultants, I. A. L. (2018). Global overview of the flavours and fragrances market (11th ed.). London: https://www.marketresearch.
com/IAL-Consultants-v3050/Global-Overview-FlavoursFragrances-11th-11788647/.
Dagne, E., Bisrat, D., Alemayehu, M., & Worku, T. (2000). Essential oils
of twelve Eucalyptus species from Ethiopia. Journal of Essential Oil
Research, 12(4), 467–470. https://doi.org/10.1080/10412905.2000.
9699567.
Dasgupta, A., Gu, Q., Hermanson, K. D., Moaddel, T., Salgaonkar, N.,
Shen, B., & Qiu, Q. (2019). EP3442493B1-An antimicrobial composition comprising thymol, terpineol and a cationic phospholipid.
European Patent Office. https://patents.google.com/patent/
EP3442493B1/en
de Carvalho, C. C. C. R. (2016). Fungi in fermentation and biotransformation systems. In D.-W. Li (Ed.), Biology of microfungi (pp. 525–
541). New York: Springer. https://doi.org/10.1007/978-3-31929137-6_21.
de Lima, R. K., das Cardoso, M. G., Andrade, M. A., Nascimento, E. A.,
de Morais, S. A. L., & Nelson, D. L. (2010). Composition of the
essential oil from the leaves of tree domestic varieties and one wild
variety of the guava plant (Psidium guajava L., Myrtaceae). Revista
Brasileira de Farmacognosia, 20(1), 41–44. https://doi.org/10.
1590/s0102-695x2010000100009.
Demyttenaere, J. C. R., Van Belleghem, K., & De Kimpe, N. (2001).
Biotransformation of (R)-(+)- and (S)-(−)-limonene by fungi and the
use of solid phase microextraction for screening. Phytochemistry,
57(2), 199–208. https://doi.org/10.1016/S0031-9422(00)00499-4.
Di Sotto, A., Durazzi, F., Sarpietro, M. G., & Mazzanti, G. (2013).
Antimutagenic and antioxidant activities of some bioflavours from
wine. Food and Chemical Toxicology, 60, 141–146. https://doi.org/
10.1016/j.fct.2013.07.042.
dos Santos Negreiros, P., da Costa, D. S., da Silva, V. G., de Carvalho
Lima, I. B., Nunes, D. B., de Melo Sousa, F. B., de Souza Lopes
Araújo, T., Medeiros, J. V. R., dos Santos, R. F., & de Cássia
Meneses Oliveira, R. (2019). Antidiarrheal activity of α-terpineol
in mice. Biomedicine and Pharmacotherapy, 110, 631–640. https://
doi.org/10.1016/j.biopha.2018.11.131.
Ehret, C., Maupetit, P., & Petrzilka, M. (1992). New organoleptically
important constituents of narcissus absolute (Narcissus poeticus
L.). Journal of Essential Oil Research, 4(1), 41–47. https://doi.org/
10.1080/10412905.1992.9698008.
Farias, W. C., Ferreira, H. D., Sá, S., Cunha, L. C., Neto, J. R. O., Borges,
L. L., Paula, J. R., & Fiuza, T. S. (2018). Evaluation of the chemical
composition and variability of the volatile oils from Trembleya
parviflora leaves. Brazilian Journal of Pharmacognosy, 28(4),
414–420. https://doi.org/10.1016/j.bjp.2018.04.009.
FEEDAP, E. P. on A. and P. or S. used in A. F. (2012). Scientific opinion
on the safety and efficacy of aliphatic, alicyclic and aromatic saturated and unsaturated tertiary alcohols and esters with esters containing tertiary alcohols ethers (chemical group 6) when used as
flavourings for all animal species. EFSA Journal, 10(11), 2966.
https://doi.org/10.2903/j.efsa.2012.2966.
Felipe, L. O., De Oliveira, A. M., & Bicas, J. L. (2017). Bioaromas–
perspectives for sustainable development. Trends in Food Science
& Technology, 62, 141–153. https://doi.org/10.1016/j.tifs.2017.02.
005.
1276
Ferhat, M. A., Meklati, B. Y., & Chemat, F. (2007). Comparison of
different isolation methods of essential oil from Citrus fruits: cold
pressing, hydrodistillation and microwave “dry” distillation.
Flavour and Fragrance Journal, 22(6), 494–504. https://doi.org/
10.1002/ffj.1829.
Gad, H. A., Ayoub, I. M., & Wink, M. (2019). Phytochemical profiling
and seasonal variation of essential oils of three Callistemon species
cultivated in Egypt. PLoS One, 14(7). https://doi.org/10.1371/
journal.pone.0219571.
Gouveia, D. N., Costa, J. S., Oliveira, M. A., Rabelo, T. K., de Silva, A.
M. O. E., Carvalho, A. A., et al. (2018). α-Terpineol reduces cancer
pain via modulation of oxidative stress and inhibition of iNOS.
Biomedicine and Pharmacotherapy, 105, 652–661. https://doi.org/
10.1016/j.biopha.2018.06.027.
Hassan, S. B., Gali-Muhtasib, H., Göransson, H., & Larsson, R. (2010).
Alpha terpineol: a potential anticancer agent which acts through
suppressing NF-κB signalling. Anticancer Research, 30(6), 1911–
1919.
He, W., Yoon, K. J., Eriksen, R. S., Gopalan, S., Basu, S. N., & Pal, U. B.
(2010). Out-of-cell measurements of H2-H2O effective binary diffusivity in the porous anode of solid oxide fuel cells (SOFCs).
Journal of Power Sources, 195(2), 532–535. https://doi.org/10.
1016/j.jpowsour.2009.07.051.
Held, S., Schieberle, P., & Somoza, V. (2007). Characterization of alphaterpineol as an anti-inflammatory component of orange juice by
in vitro studies using oral buccal cells. Journal of Agricultural and
Food Chemistry, 55(20), 8040–8046. https://doi.org/10.1021/
jf071691m.
Ireland, B. F., Hibbert, D. B., Goldsack, R. J., Doran, J. C., & Brophy, J.
J. (2002). Chemical variation in the leaf essential oil of Melaleuca
quinquenervia (Cav.) S.T. Blake. Biochemical Systematics and
Ecology, 30(5), 457–470. https://doi.org/10.1016/S0305-1978(01)
00112-0.
ISO 4730. (2017). ISO 4730:2017-Essential oil of Melaleuca, terpinen-4ol type (tea tree oil) (3rd ed.). Geneva: Organização Internacional de
Normalização. https://www.iso.org/standard/69082.html
JECFA. (1998). Evaluations of the Joint FAO/WHO Expert Committee
on Food Additives (JECFA). http://apps.who.int/food-additivescontaminants-jecfa-database/chemical.aspx?chemID=5040.
Accessed 1 January 2019.
Jeleń, H. H. H., Majcher, M., & Dziadas, M. (2012). Microextraction
techniques in the analysis of food flavor compounds: a review.
Analytica Chimica Acta, 738, 13–26. https://doi.org/10.1016/j.aca.
2012.06.006.
Jirovetz, L., Buchbauer, G., Denkova, Z., Stoyanova, A., Murgov, I.,
Schmidt, E., & Geissler, M. (2005). Antimicrobial testings and gas
chromatographic analysis of pure oxygenated monoterpenes 1,8cineole, α-terpineol, terpinen-4-ol and camphor as well as target
compounds in essential oils of pine (Pinus pinaster), rosemary
(Rosmarinus officinalis), tea tree. Scientia Pharmaceutica, 73(1),
27–38. https://doi.org/10.3797/scipharm.aut-05-03.
Jongedijk, E., Cankar, K., Buchhaupt, M., Schrader, J., Bouwmeester,
H., & Beekwilder, J. (2016). Biotechnological production of
limonene in microorganisms. Applied Microbiology and
Biotechnology, 100(7), 2927–2938. https://doi.org/10.1007/
s00253-016-7337-7.
Khaleel, C., Tabanca, N., & Buchbauer, G. (2018). α-Terpineol, a natural
monoterpene: a review of its biological properties. Open Chemistry,
16(1), 349–361. https://doi.org/10.1515/chem-2018-0040.
Khodabakhsh, P., Shafaroodi, H., & Asgarpanah, J. (2015). Analgesic
and anti-inflammatory activities of Citrus aurantium L. blossoms
essential oil (neroli): involvement of the nitric oxide/cyclicguanosine monophosphate pathway. Journal of Natural
Medicines, 69(3), 324–331. https://doi.org/10.1007/s11418-0150896-6.
Food Bioprocess Technol (2020) 13:1261–1279
Koetzle, R. A. (2004). US20060081822A1 - Method to increase flash
points of flammable solvents. USA. https://patents.google.com/
patent/US20060081822
Kong, J.-O., Lee, S.-M., Moon, Y.-S., Lee, S.-G., & Ahn, Y.-J. (2007).
Nematicidal activity of cassia and cinnamon oil compounds and
related compounds toward Bursaphelenchus xylophilus
(Nematoda: Parasitaphelenchidae). Journal of Nematology, 39(1),
31–36 http://www.ncbi.nlm.nih.gov/pubmed/19259472%0A http://
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=
PMC2586484.
Kong, Q., Zhang, L., An, P., Qi, J., Yu, X., Lu, J., & Ren, X. (2019).
Antifungal mechanisms of α-terpineol and terpene-4-alcohol as the
critical components of Melaleuca alternifolia oil in the inhibition of
rot disease caused by Aspergillus ochraceus in postharvest grapes.
Journal of Applied Microbiology, 126(4), 1161–1174. https://doi.
org/10.1111/jam.14193.
Kraidman, G., Mukherjee, B. B., & Hill, I. D. (1969). Conversion of Dlimonene into an optically active isomer of α-terpineol by a
Cladosporium species. Bacteriol. Proc., 69, 63.
Kreis, P., & Mosandl, A. (1993). Chiral compounds of essential oils. Part
XIII. Simultaneous chirality evaluation of geranium oil constituents.
Flavour and Fragrance Journal, 8(3), 161–168. https://doi.org/10.
1002/ffj.2730080307.
Lee, S. Y., Kim, S. H., Hong, C. Y., Park, S. Y., & Choi, I. G. (2015).
Biotransformation of (−)-α-pinene and geraniol to α-terpineol and
p-menthane-3,8-diol by the white rot fungus, Polyporus brumalis.
Journal of Microbiology, 53(7), 462–467. https://doi.org/10.1007/
s12275-015-5081-9.
Li, J., Perdue, E. M., Pavlostathis, S. G., & Araujo, R. (1998).
Physicochemical properties of selected monoterpenes.
Environment International, 24(3), 353–358. https://doi.org/10.
1016/S0160-4120(98)00013-0.
Liu, X. C., Li, Y. P., Li, H. Q., Deng, Z. W., Zhou, L., Liu, Z. L., & Du, S.
S. (2013). Identification of repellent and insecticidal constituents of
the essential oil of Artemisia rupestris L. aerial parts against
liposcelis bostrychophila Badonnel. Molecules, 18(9), 10733–
10746. https://doi.org/10.3390/molecules180910733.
Malizia, R. A., Molli, J. S., Cardell, D. A., & Retamar, J. A. (1996).
Essential oil of mentha citrata grown in Argentina. Variation in the
composition and yield at full- and post-flowering. Journal of
Essential Oil Research, 8(4), 347–349. https://doi.org/10.1080/
10412905.1996.9700637.
Margetts, J. (2004). Aroma chemicals V: natural aroma chemicals. In D.
J. Rowe (Ed.), Chemistry and technology of flavours and fragrances
(pp. 169–198). Hoboken: Blackwell Publishing Ltd.. https://doi.org/
10.1002/9781444305517.ch8.
Markin, A. V., Smirnova, N. N., Il’Ichev, I. S., Dolinsky, T. I., & Radbil,
A. B. (2016). Thermodynamic properties of α-terpineol over the
range from T → (0 to 345) K. Journal of Thermal Analysis and
Calorimetry, 123(2), 1451–1458. https://doi.org/10.1007/s10973015-5068-0.
Marnett, L. J., Cohen, S. M., Fukushima, S., Gooderham, N. J., Hecht, S.
S., Rietjens, I. M. C. M., Smith, R. L., Adams, T. B., Bastaki, M.,
Harman, C. L., McGowen, M. M., & Taylor, S. V. (2014). GRASr2
evaluation of aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances used as flavoring ingredients. Journal of Food Science, 79(4), R428–R441. https://doi.org/
10.1111/1750-3841.12407.
Maróstica Jr., M. R., Silva, T. A. A. R., e Franchi, G. C., Nowill, A.,
Pastore, G. M., & Hyslop, S. (2009). Antioxidant potential of aroma
compounds obtained by limonene biotransformation of orange essential oil. Food Chemistry, 116(1), 8–12. https://doi.org/10.1016/j.
foodchem.2009.01.084.
Maróstica, M. R., & Pastore, G. M. (2007). Production of R-(+)-α-terpineol by the biotransformation of limonene from orange essential
Food Bioprocess Technol (2020) 13:1261–1279
oil, using cassava waste water as medium. Food Chemistry, 101(1),
345–350. https://doi.org/10.1016/j.foodchem.2005.12.056.
Matasyoh, J. C., Kiplimo, J. J., Karubiu, N. M., & Hailstorks, T. P.
(2007). Chemical composition and antimicrobial activity of essential
oil of Tarchonanthus camphoratus. Food Chemistry, 101(3), 1183–
1187. https://doi.org/10.1016/j.foodchem.2006.03.021.
McGorrin, R. J. (2002). Character impact compounds: flavors and offflavors in foods. In R. Marsili (Ed.), Flavor, fragrance, and odor
analysis (2nd ed., pp. 207–262). New York: Marcel Dekker.
Miguel, G., Simões, M., Figueiredo, A. C., Barroso, J. G., Pedro, L. G., &
Carvalho, L. (2004). Composition and antioxidant activities of the
essential oils of Thymus caespititius, Thymus camphoratus and
Thymus mastichina. Food Chemistry, 86(2), 183–188. https://doi.
org/10.1016/j.foodchem.2003.08.031.
Milojević, S. Ž., Stojanović, T. D., Palić, R., Lazić, M. L., & Veljković,
V. B. (2008). Kinetics of distillation of essential oil from comminuted ripe juniper (Juniperus communis L.) berries. Biochemical
Engineering Journal, 39(3), 547–553. https://doi.org/10.1016/j.bej.
2007.10.017.
Mimoune, N. A., Mimoune, D. A., & Yataghene, A. (2013). Chemical
composition and antimicrobial activity of the essential oils of Pinus
pinaster. Journal of Coastal Life Medicine, 1(1), 54–58. https://doi.
org/10.12980/jclm.1.20133d322.
Mitchell, R. F., Ray, A. M., Hanks, L. M., & Millar, J. G. (2018). The
common natural products (S)-α-terpineol and (e)-2-hexenol are important pheromone components of Megacyllene antennata
(Coleoptera: Cerambycidae). Environmental Entomology, 47(6),
1547–1552. https://doi.org/10.1093/ee/nvy126.
Molina, G., Pessôa, M. G., Bicas, J. L., Fontanille, P., Larroche, C., &
Pastore, G. M. (2019). Optimization of limonene biotransformation
for the production of bulk amounts of α-terpineol. Bioresource
Technology, 122180, 122180. https://doi.org/10.1016/j.biortech.
2019.122180.
Monti, D., Chetoni, P., Burgalassi, S., Najarro, M., Saettone, M. F., &
Boldrini, E. (2002). Effect of different terpene-containing essential
oils on permeation of estradiol through hairless mouse skin.
International Journal of Pharmaceutics, 237(1–2), 209–214. https://
doi.org/10.1016/S0378-5173(02)00032-7.
Muchtaridi Subarnas, A., Apriyantono, A., & Mustarichie, R. (2010).
Identification of compounds in the essential oil of nutmeg seeds
(Myristica fragrans Houtt.) that inhibit locomotor activity in mice.
International Journal of Molecular Sciences, 11(11), 4771–4781.
https://doi.org/10.3390/ijms11114771.
Nasser AL-Jabri, N., & Hossain, M. A. (2014). Comparative chemical
composition and antimicrobial activity study of essential oils from
two imported lemon fruits samples against pathogenic bacteria.
Beni-Suef University Journal of Basic and Applied Sciences, 3(4),
247–253. https://doi.org/10.1016/j.bjbas.2014.10.011.
Nogueira, M. N. M., Aquino, S. G., Rossa, C., & Spolidorio, D. M. P.
(2014). Terpinen-4-ol and alpha-terpineol (tea tree oil components)
inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages. Inflammation Research, 63(9), 769–778. https://doi.org/10.
1007/s00011-014-0749-x.
Noma, Y., & Asakawa, Y. (2010). Biotransformation of monoterpenoids.
In Comprehensive Natural Products II: Chemistry and Biology
(Vol. 3, pp. 669–801). Elsevier. https://doi.org/10.1016/B978008045382-8.00742-5.
Noma, Y., & Asakawa, Y. (2015). Biotransformation of monoterpenoids
by microorganisms, insects, and mammals. In Handbook of essential oils: science, technology, and applications, second edition (pp.
747–905). https://doi.org/10.1201/b19393.
Northover, B. J., & Verghese, J. (1962). The pharmacology of certain
terpene alcohols and oxides. Journal of Scientific and Industrial
Research, 21C, 342–345.
Novak, J., Lukas, B., & Franz, C. M. (2008). The essential oil composition of wild growing sweet marjoram (origanum majorana L.,
1277
lamiaceae) from cyprus—three chemotypes. Journal of Essential
Oil Research, 20(4), 339–341. https://doi.org/10.1080/10412905.
2008.9700026.
NPCS Board of Consultants & Engineers, N. B. of C. & E. (2010).
Industrial alcohol technology handbook. Delhi: Asia Pacific
Business Press Inc..
Peana, A., Moretti, M., & Juliano, C. (1999). Chemical composition and
antimicrobial action of the essential oils of Salvia desoleana and S.
sclarea. Planta Medica, 65(08), 752–754. https://doi.org/10.1055/s2006-960857.
Penfold, A. R., & Grant, R. (1925). The germicidal values of some
Australian essential oils and their pure constituents, together with
those of some essential oil isolates and synthetics Part III. Journal
Royal Society of New South Wales, 58, 346–350.
Périno-Issartier, S., Ginies, C., Cravotto, G., & Chemat, F. (2013). A
comparison of essential oils obtained from lavandin via different
extraction processes: ultrasound, microwave, turbohydrodistillation,
steam and hydrodistillation. Journal of Chromatography A, 1305,
41–47. https://doi.org/10.1016/j.chroma.2013.07.024.
Pina, L. T. S., Ferro, J. N. S., Rabelo, T. K., Oliveira, M. A., Scotti, L.,
Scotti, M. T., Walker, C. I. B., Barreto, E. O., Quintans Júnior, L. J.,
& Guimarães, A. G. (2019). Alcoholic monoterpenes found in essential oil of aromatic spices reduce allergic inflammation by the
modulation of inflammatory cytokines. Natural Product Research,
33(12), 1773–1777. https://doi.org/10.1080/14786419.2018.
1434634.
Prakoso, T., Hanley, J., Soebianta, M. N., Soerawidjaja, T. H., & Indarto,
A. (2018). Synthesis of terpineol from α-pinene using low-price
acid catalyst. Catalysis Letters, 148(2), 725–731. https://doi.org/
10.1007/s10562-017-2267-2.
Prasad, C., Imrhan, V., Juma, S., Maziarz, M., Prasad, A., Tiernan, C., &
Vijayagopal, P. (2015). Bioactive plant metabolites in the management of non-communicable metabolic diseases: looking at opportunities beyond the horizon. Metabolites, 5(4), 733–765. https://doi.
org/10.3390/metabo5040733.
Prieto, J. M., Iacopini, P., Cioni, P., & Chericoni, S. (2007). In vitro
activity of the essential oils of Origanum vulgare, Satureja montana
and their main constituents in peroxynitrite-induced oxidative processes. Food Chemistry, 104(3), 889–895. https://doi.org/10.1016/j.
foodchem.2006.10.064.
Putievsky, E., Dudai, N., Ravid, U., Katzir, I., Michaelovich, Y., Zuabi,
E., & Saadi, D. (1996). Morphology, phenology, and essential oil of
micromeria fruticosa (L.) druce in different seasons. Journal of
Herbs Spices & Medicinal Plants, 3(3), 27–34. https://doi.org/10.
1300/J044v03n03_05.
Quintans-Júnior, L. J., Oliveira, M. G. B. B., Santana, M. T. M. F. M. T.,
Santana, M. T. M. F. M. T., Guimarães, A. G., Siqueira, J. S., et al.
(2011). α-Terpineol reduces nociceptive behavior in mice.
Pharmaceutical Biology, 49(6), 583–586. https://doi.org/10.3109/
13880209.2010.529616.
Ravid, U., Putievsky, E., & Katzir, I. (1995). Determination of the enantiomeric composition of α-terpineol in essential oils. Flavour and
Fragrance Journal, 10(4), 281–284. https://doi.org/10.1002/ffj.
2730100409.
Ribeiro, P. V. M., Andrade, P. A., Hermsdorff, H. H. M., dos Santos, C.
A., Cotta, R. M. M., de Estanislau, J. A. S. G., et al. (2019). Dietary
non-nutrients in the prevention of non-communicable diseases: potentially related mechanisms. Nutrition, 66, 22–28. https://doi.org/
10.1016/j.nut.2019.03.016.
Richard, H., & Murray, G. (1958). US2898380A - Production of alphaterpineol. USA. https://patents.google.com/patent/US2898380
RIFM. (1984). 14-day single dose subacute toxicity study with alphaterpineol.
Rottava, I., Toniazzo, G., Cortina, P. F., Martello, E., Grando, C. E.,
Lerin, L. A., Treichel, H., Mossi, A. J., de Oliveira, D., Cansian,
R. L., Antunes, O. A. C., & Oestreicher, E. G. (2010). Screening of
1278
microorganisms for bioconversion of (−)β-pinene and R-(+)-limonene to α-terpineol. LWT - Food Science and Technology, 43(7),
1128–1131. https://doi.org/10.1016/j.lwt.2010.03.001.
Rottava, I., Cortina, P. F., Martello, E., Cansian, R. L., Toniazzo, G.,
Antunes, O. A. C., Oestreicher, E. G., Treichel, H., & de Oliveira,
D. (2011). Optimization of α-terpineol production by the biotransformation of R-(+)-limonene and (−)-β-pinene. Applied
Biochemistry and Biotechnology, 164(4), 514–523. https://doi.org/
10.1007/s12010-010-9153-3.
Rozenbaum, H. F., Patitucci, M. L., Antunes, O. A. C., & Pereira, N.
(2006). Production of aromas and fragrances through microbial oxidation of monoterpenes. Brazilian Journal of Chemical
Engineering, 23(3), 273–279. https://doi.org/10.1590/S010466322006000300001.
Safaripour, S., Nemati, Y., Parvardeh, S., Ghafghazi, S., Fouladzadeh, A.,
& Moghimi, M. (2018). Role of l-arginine/SNAP/NO/cGMP/KATP
channel signalling pathway in antinociceptive effect of α-terpineol
in mice. Journal of Pharmacy and Pharmacology, 70(4), 507–515.
https://doi.org/10.1111/jphp.12864.
Sakasegawa, M., Hori, K., & Yatagai, M. (2003). Composition and
antitermite activities of essential oils from Melaleuca species.
Journal of Wood Science, 49(2), 181–187. https://doi.org/10.1007/
s100860300029.
Sales, A., Paulino, B. N., Pastore, G. M., & Bicas, J. L. (2018).
Biogeneration of aroma compounds. Current Opinion in Food
Science, 19, 77–84. https://doi.org/10.1016/j.cofs.2018.03.005.
Savithiry, N., Cheong, T. K., & Oriel, P. (1997). Production of αterpineol from Escherichia coli cells expressing thermostable limonene hydratase. In B. H. Davison, C. E. Wyman, & M. Finkelstein
(Eds.), Biotechnology for fuels and chemicals. Applied biochemistry
and biotechnology (pp. 213–220). Totowa: Humana Press Inc..
https://doi.org/10.1007/978-1-4612-2312-2_20.
Scifinder®. (2019). Scifinder - Chemical Abstracts Service. https://
scifinder.cas.org. Accessed 1 April 2019.
Sell, C. S. (2006). Ingredients for the modern perfumery industry. In D.
Pybus & C. Sell (Eds.), The chemistry of fragrances (2nd ed., pp.
52–131). London: Royal Society of Chemistry. https://doi.org/10.
1039/9781847555342-00052.
Sell, C. S., & Pybus, D. H. (2006). The history of aroma chemistry and
perfume. In D. Pybus & C. Sell (Eds.), The chemistry of fragrances
(2nd ed., pp. 3–23). London: Royal Society of Chemistry. https://
doi.org/10.1039/9781847555342-00003.
Siddhardha, B., Vijay Kumar, M., Murty, U. S. N. S. N., Ramanjaneyulu,
G. S. S., Prabhakar, S., Kumar, M. V., et al. (2012).
Biotransformation of α-pinene to terpineol by resting cell suspension of Absidia corulea. Indian Journal of Microbiology, 52(2),
292–294. https://doi.org/10.1007/s12088-011-0155-9.
Smith, S. W. (2009). Chiral toxicology: it’s the same thing only different.
Toxicological Sciences, 110(1), 4–30. https://doi.org/10.1093/
toxsci/kfp097.
Sousa, D., Quintans, L., & de Almeida, R. (2007a). Evolution of the
anticonvulsant activity of α-terpineol. Pharmaceutical Biology,
45(1), 69–70. https://doi.org/10.1080/13880200601028388.
Sousa, D., Raphael, E., Brocksom, U., & Brocksom, T. (2007b). Sedative
effect of monoterpene alcohols in mice: a preliminary screening.
Zeitschrift fur Naturforschung - Section C Journal of Biosciences,
62(7–8), 563–566.
Sousa, G. M., Cazarin, C. B. B., Marostica Junior, M. R., Lamas, C. A.,
Quitete, V. H. A. C., Pastore, G. M., Bicas, J. L. (2020). The effect
of α-terpineol enantiomers on biomarkers of rats fed a high fat-diet.
Heliyon - Food Science. 6(4), e03752. https://doi.org/10.1016/j.
heliyon.2020.e03752.
Surburg, H., & Panten, J. (2016). Common fragrance and flavor materials: preparation, properties and uses. (H. Surburg & J. Panten,
Eds.)Common fragrance and flavor materials: preparation,
Food Bioprocess Technol (2020) 13:1261–1279
properties and uses (6nd ed.). Weinheim: Wiley-VCH. https://doi.
org/10.1002/9783527693153.
Tadtong, S., Kamkaen, N., Watthanachaiyingcharoen, R., &
Ruangrungsi, N. (2015). Chemical components of four essential oils
in aromatherapy recipe. Natural Product Communications, 10(6),
1091–1092.
Tai, Y. N., Xu, M., Ren, J. N., Dong, M., Yang, Z. Y., Pan, S. Y., & Fan,
G. (2016). Optimisation of α-terpineol production by limonene biotransformation using Penicillium digitatum DSM 62840. Journal of
the Science of Food and Agriculture, 96(3), 954–961. https://doi.
org/10.1002/jsfa.7171.
Tan, Q., & Day, D. F. (1998). Bioconversion of limonene to a-terpineol
by immobilized Penicillium digitatum. Applied Microbiology and
Biotechnology, 49(1), 96–101. https://doi.org/10.1007/
s002530051143.
Tan, Q., Day, D. F., & Cadwallader, K. R. (1998). Bioconversion of (R)(+)-limonene by P. digitatum (NRRL 1202). Process Biochemistry,
33(1), 29–31. https://doi.org/10.1016/S0032-9592(97)00048-4.
Teodoro, A. J. (2019). Bioactive compounds of food: their role in the
prevention and treatment of diseases. Oxidative Medicine and
Cellular Longevity, 2019, 1–4. https://doi.org/10.1155/2019/
3765986.
The Good Scents Company Information System. (2019). The good scents
company information system. https://doi.org/10.2903/j.efsa.2010.
1400, 8, 10.
Toniazzo, G., de Oliveira, D., Dariva, C., Oestreicher, E. G., & Antunes,
O. A. C. (2005). Biotransformation of (−)β-pinene by Aspergillus
niger ATCC 9642. Applied Biochemistry and Biotechnology,
123(1–3), 0837–0844. https://doi.org/10.1385/abab:123:1-3:0837.
Tsokou, A., Georgopoulou, K., Melliou, E., Magiatis, P., & Tsitsa, E.
(2007). Composition and enantiomeric analysis of the essential oil
of the fruits and the leaves of Pistacia vera from Greece. Molecules,
12(6), 1233–1239. https://doi.org/10.3390/12061233.
US FDA. (2018). 21CFR172.515 - title 21 - food and drugs - chapter I subchapter B - part 172 - food additives permitted for direct addition
to food for human consumption.
Vallinayagam, R., Vedharaj, S., Naser, N., Roberts, W. L. L., Dibble, R.
W. W., & Sarathy, S. M. M. (2017). Terpineol as a novel octane
booster for extending the knock limit of gasoline. Fuel, 187, 9–15.
https://doi.org/10.1016/j.fuel.2016.09.034.
Vespermann, K. A. C., Paulino, B. N., Barcelos, M. C. S., Pessôa, M. G.,
Pastore, G. M., & Molina, G. (2017). Biotransformation of α- and
β-pinene into flavor compounds. Applied Microbiology and
Biotechnology, 101(5), 1805–1817. https://doi.org/10.1007/
s00253-016-8066-7.
Werkhoff, P., Brennecke, S., Bretschneider, W., Güntert, M., Hopp, R., &
Surburg, H. (1993). Chirospecific analysis in essential oil, fragrance
and flavor research. Zeitschrift für Lebensmittel-Untersuchung und Forschung, 196(4), 307–328. https://doi.org/10.1007/BF01197930.
Whish, J. P. M., & Williams, R. R. (1996). Effects of post harvest drying
on the yield of tea tree oil (Melaleuca alternifolia). Journal of
Essential Oil Research, 8(1), 47–51. https://doi.org/10.1080/
10412905.1996.9700552.
Wijayati, N., Hidayah, N., Mursiti, S., & Kusumastuti, E. (2019).
Catalytic activity of P 2 O 5-natural zeolite on hydration reaction
of turpentine into α-terpineol. IOP Conference Series: Materials
Science and Engineering, 509(1). https://doi.org/10.1088/1757899X/509/1/012093.
Wilson, R. A., Butler, J. F., Withycombe, D. A., Mookherjee, B. D., Katz,
I., & Schrankel, K. R. (1989). US4886662A - Use of alpha-terpineol
as insect attractant. USA. https://patents.google.com/patent/
US4886662A/en
Wong, Y. C., Ahmad-Mudzaqqir, M. Y., & Wan-Nurdiyana, W. A.
(2014). Extraction of essential oil from cinnamon (Cinnamomum
zeylanicum). Oriental Journal of Chemistry, 30(1), 37–47. https://
doi.org/10.13005/ojc/300105.
Food Bioprocess Technol (2020) 13:1261–1279
Wright, S. J., Caunt, P., Carter, D., & Baker, P. B. (1986). Microbial
oxidation of alpha-pinene by Serratia marcescens. Applied
Microbiology and Biotechnology, 23(3–4), 224–227. https://doi.
org/10.1007/BF00261919.
Yamahara, J., Kimura, H., Kobayashi, M., Okamoto, T., Sawada, T.,
Fujimura, H., & Chisaka, T. (1985). Cholagogic action and characteristics of (±)-α-terpineol-β-D-O-glucopyranoside, a new
monoterpenoid glucoside. Chemical and Pharmaceutical Bulletin,
33(4), 1669–1675. https://doi.org/10.1248/cpb.33.1669.
Yi, D., Xu, H., Hou, Y., Wang, L., Zhao, D., Wu, T., et al. (2018).
PSX-12 effects of dietary supplementation with α-terpineol on
growth performance and intestinal functions in piglets challenged with recombinant E. coli strain LMG194-STa. Journal
of Animal Science, 96(suppl_3), 484–484. https://doi.org/10.
1093/jas/sky404.1057.
Yoo, S. K. K., & Day, D. F. F. (2002). Bacterial metabolism of α- and βpinene and related monoterpenes by Pseudomonas sp. strain PIN.
Process Biochemistry, 37(7), 739–745. https://doi.org/10.1016/
S0032-9592(01)00262-X.
Yoo, S. K. K., Day, D. F. F., & Cadwallader, K. R. R. (2001).
Bioconversion of α- and β-pinene by Pseudomonas sp. strain PIN.
Process Biochemistry, 36(10), 925–932. https://doi.org/10.1016/
S0032-9592(00)00248-X.
Yoon, K. J., Zink, P., Gopalan, S., & Pal, U. B. (2007a). Polarization
measurements on single-step co-fired solid oxide fuel cells
(SOFCs). Journal of Power Sources, 172(1), 39–49. https://doi.
org/10.1016/j.jpowsour.2007.03.003.
1279
Yoon, K. J., Zink, P., Pal, U. B., Gopalan, S., & Seccombe, D. (2007b).
High performance low cost co-fired solid oxide fuel cells. ECS
Transactions, 7(1), 579–588. https://doi.org/10.1149/1.2729139.
Zhang, Y. J., Gan, R. Y., Li, S., Zhou, Y., Li, A. N., Xu, D. P., & Li, H. B.
(2015). Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules, 20(12), 21138–21156.
https://doi.org/10.3390/molecules201219753.
Zhang, Y., Li, D., Wang, Z., Zang, W., Rao, P., Liang, Y., & Mei, Y.
(2018). Alpha-terpineol affects synthesis and antitumor activity of
triterpenoids from Antrodia cinnamomea mycelia in solid-state culture. Food & Function, 9(12), 6517–6525. https://doi.org/10.1039/
c8fo02079e.
Zhang, C., Li, M., Zhao, G.-R., & Lu, W. (2019). Alpha-terpineol production from an engineered Saccharomyces cerevisiae cell factory.
Microbial Cell Factories, 18, 160. https://doi.org/10.1186/s12934019-1211-0.
Zhou, H., Tao, N., & Jia, L. (2014). Antifungal activity of citral, octanal
and α-terpineol against Geotrichum citri-aurantii. Food Control.
https://doi.org/10.1016/j.foodcont.2013.09.057.
Zhu, W., Liu, X., Wang, Y., Tong, Y., & Hu, Y. (2018). Discovery of a
novel series of α-terpineol derivatives as promising anti-asthmatic
agents: their design, synthesis, and biological evaluation. European
Journal of Medicinal Chemistry, 143, 419–425. https://doi.org/10.
1016/j.ejmech.2017.07.068.
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.