Table 5: Synthetic pathways based on isoprenoids, listed in chronological order
Host organism
Engineering steps
1)
Saccharomyces
cerevisiae
2)
1)
Candida utilis
2)
Introduction of the Erwinia uredovora carotenoid
biosynthesis genes [216] crtE, crtB, crtI and crtY (
-carotene) and crtE, crtB and crtI ( lycopene),
respectively, under the control of S. cerevisiae
promoters and terminators [221]
Introduction of Erwinia herbicola carotenoid
biosynthesis genes for lycopene, -carotene and
zeaxanthin production under the control of S.
cerevisiae promoters and terminators [222]
Introduction of synthetic, codon-optimized Erwinia
uredovora carotenoid biosynthesis genes (crtE, crtB,
crtI and crtY) [216] and Agrobacterium aurantiacum
carotenoid biosynthesis genes (crtZ and crtW) [217]
under the control ot C. utilis promoters and
terminators:
– Astaxanthin: crtE, crtB, crtI, crtY, crtZ and crtW
– -Carotene: crtE, crtB, crtI and crtY
– Lycopene: crtE, crtB and crtI
Improving Lycopene yields [218] by disruption of the
C. utilis squalene synthase gene (ERG9) and overexpression of the catalytic domain of the C. utilis 3hydroxy methylglutaryl CoA reductase gene (HMG)
Substrate
Product / Outcome
CH3
CH3
H3C
CH3
CH3
Ref
H3C
CH3
CH3
CH3
[221-223]
CH3
-Carotene: 0.103 mg/g [CDW]
CH3
CH3
H3C
CH3
H3C
CH3
galactose
CH3
H3C
CH3
HO
CH3
[221-223]
CH3
Lycopene: 0.113 mg/g [CDW]
CH3
CH3
H3C
CH3
CH3
CH3
OH
H3C
CH3
CH3
[222,223]
Zeaxanthin: 0.01% of CDW
~0.2 - 0.05 mg/g [CDW]
CH3
CH3
H3C
CH3
OH
H3C
O
O
CH3
HO
CH3
CH3
CH3
CH3
[219]
Astaxanthin: 0.4 mg/g [CDW]
CH3
CH3
H3C
CH3
H3C
CH3
CH3
CH3
glucose
CH3
CH3
[219]
-Carotene: 0.4 mg/g [CDW]
CH3
CH3
H3C
CH3
H3C
CH3
CH3
CH3
CH3
CH3
[218,219]
Lycopene: 1.1 mg/g [CDW][219]
7.8 mg/g [CDW][218]
O
1)
Saccharomyces
cerevisiae (fen1)
2)
3)
1)
Saccharomyces
cerevisiae (fen1)
2)
3)
4)
1)
2)
Saccharomyces
cerevisiae
3)
4)
1)
Saccharomyces
cerevisiae
2)
3)
4)
1)
Saccharomyces
cerevisiae
2)
Transfer of expression cassettes for mature bovine
adrenodoxin (ADX), adrenodoxin reductase (ADR),
and side chain cleavage cytochrome P450 (P450scc)
Transfer of Arabidopsis thaliana 7-sterol reductase
Disruption of 22-sterol desaturase (one step of
endogenous ergosterol biosynthetic pathway)
Transfer of expression cassettes for mature bovine
adrenodoxin (ADX), adrenodoxin reductase (ADR),
and side chain cleavage cytochrome P450 (P450scc)
Transfer of Arabidopsis thaliana 7-sterol reductase
Disruption of 22-sterol desaturase (one step of
endogenous ergosterol biosynthetic pathway)
Introduction of type II human 3-hydroxy-steroid
dehydrogenase-isomerase (3-HSD)
Rerouting the ergosterol biosynthesis pathway
Introduction of the mammalian-specific part of the
hydrocortisone biosynthetic pathway
Inactivation of side reactions to steroid biosynthesis
dead ends
Adjusting expression levels for optimized steroid
channeling to hydrocortisone
Introduction of the Artemisia annua epi-cedrol
synthase gene
Overexpression of a truncated Hydroxy-methylglutaryl
CoA reductase (trHmg1p)
Mutation of the Upc2p transcription factor 
introduction of the upc2-1 allele with G888D [242]
Employing the S.c. haploid mating type a
Introduction of five Taxol biosynthetic genes from
Taxus species: geranylgeranyl disphosphate synthase (GGPPS), taxadiene synthase (TS), taxadiene 5hydroxylase (THY5a), taxadienol 5-O-acetyl transferase (TAT), taxoid 10-hydroxylase (THY10b) with
necessary modifications for the expression in S. c.
Due to restricted THY5a expression, only a very small
amount of the intermediate taxadien-5-ol and no
taxadien-5-acetoxy-10-ol was detected in vivo [230]
CH3
galactose
H
Saccharomyces
cerevisiae
2)
3)
Engineering the farnesyl pyrophosphate (FPP)
biosynthetic pathway
Introduction of the Artemisia annua L amorphadiene
synthase gene (FPP  amorphadiene)
Cloning the A. annua CYP71AV1/CPR (3-step
oxidation: amorphadiene  artemisinic acid)
[241]
H
H
HO
60 mg/L
Pregnenolone
O
CH3
CH3
CH3
galactose
H
[241]
H
H
O
No value given
Progesterone
OH
O
CH3
HO
glucose /
ethanol
OH
CH3
H
H
[228]
H
O
11.5 mg/L
Hydrocortisone
OH
H3C
CH3
galactose
[229]
CH3
H3C
Epi-cedrol
simple
sugar
(glucose,
galactose)
and [2-14C]
mevalonic
acid for
radio-HPLC
analysis
HO
H3C
simple
sugar
0.37 mg/L
H3C
CH3
H3C
OAc
H
CH2
H
[230]
Taxa-4(20),11(12)-dien-5-acetoxy-10-ol
taxadien-5-ol: 0.025 mg/L
no taxadien-5-acetoxy-10-ol in vivo
CH3
H
1)
CH3
CH3
H3C
~ 32 mg/L
H
HO
[226]
CH2
O
Artemisinic acid
1)
2)
Saccharomyces
cerevisiae
Follow-up study of [226]:
Engineering the pyruvate dehydrogenase bypass
(pyruvate to acetyl-CoA) by overexpression of
– Salmonella acetyl-CoA synthetase variant (L641P)
– S. cerevisiae cytosolic acetaldehyde dehydrogenase (ALD6)
– In strain S. cerevisiae EPY224 [226]
3) Results: increased levels of mevalonate and amorpha4,11-diene (~120 mg/L); generally applicable for
isoprenoid production
OH O
H3C
HO
O
-
~380 mg/L
Mevalonate
H
CH3
glucose
[227]
H3C
~120 mg/L
H
H3C
CH2
Amorpha-4,11-diene