Center for Microbial Metabolism and Metabolic Engineering
Institute of Microbiology
Chinese Academy of Sciences
Tel: 86-10-64807461
E-mail: tanhr@im.ac.cn
Research Area
Huarong Tan
Ph.D., Professor
Molecular biology of Streptomyces. Especially，expression and regulation of genes
involved in the differentiation and secondary metabolism of Streptomyces.
Education & Professional Experience
Principle Investigator and deputy Director of Institute of Microbiology, CAS, He
obtained his Ph.D. in 1991 from the University of East Anglia and John Innes Centre,
Norwich, UK. He is a vice President of Chinese Society for Microbiology.
Current Research
Differentiation and secondary metabolism of Streptomyce
Several genes, sanJ, sanU and sanV were cloned and sequenced from Streptomyces
ansochromogenes. Gene disruption and genetic complementation revealed that these
genes were involved in nikkomycin biosynthesis. Recombinant strains were constructed
by increasing an extra copy of sanU and sanV in Streptomyces ansochromogenes.
Nikkomycin production of the recombinant strain was about 2 fold higher than that of
wild-type strain. The sanU and sanV were expressed in E. coli BL21 (DE3) and their
encoded products were purified and integrated with coenzyme B12 to form an enzyme
complex in vitro, which showed glutamate mutase activity. Experimental results showed
that SanU is the coenzyme B12 binding component. The optimal pH and temperature for
the enzyme are 7.5-8.5 and 35℃-42℃, respectively. The Km for
L-threo-β-Methylaspartic acid is about 5.2 mM. Sulfhydryl compounds are important
for activity of the reassembled enzyme. The glutamate mutase catalyzes L-glutamate
converted to L-threo-β-Methylaspartic acid, and then L-threo-β-Methylaspartic acid was
probably deaminated to form 2-oxo-3-methylsuccinic acid to join biosynthetic pathway
of the peptidyl moiety HPHT in S. ansochromogenes.
A pathway-specific transcriptional regulatory gene, sanG was cloned and sequenced
from Streptomyces ansochromogenes. Disruption of sanG abolished nikkomycin
biosynthesis. This phenotype was complemented by a single copy of sanG which was
integrated into the chromosome. Like most pathway-specific transcriptional regulatory
gene, the introduction of multiple copies of sanG resulted in about 3 fold increased
nikkomycin production. The result suggested that sanG encodes a transcriptional
activator important for nikkomycin biosynthesis that， unusually， also has pleiotropic
effects on secondary metabolism and development in Streptomyces.
Selected publications
1
Tan Huarong, and Keith Chater. 1993. Two developmentaly
controlled promoters of Streptomyces coelicolor A3(2) that
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resemble the major class of motility—related promoters in
other Bacteria. Journal of Bacteriology , 175(4): 933-940.
2 Tan Huarong Tian Yuqing Yang Haihua Wu Wei and Keith
Chater. 1996. High-level expression of whiG -A key gene
related to Streptomyces differentiation in E. coli . Science
in China (Series C) , 39 （ 3 ） : 284-290.
3 Tan Huarong Yang Haihua Tian Yuqing Wu Wei Dong Kening and
Chater Keith. 1996. Gene controlled by promoter---PTH4
depending on whiG of Streptomyces coelicolor . Science in
China (Series C) , 39 (6): 608-616.
4 Yang Haihua Tian Yuqing Tan Huarong * . 1996. Discovery
and primary study on lon gene in Streptomyces . Chinese
Science Bulletin , 41 （ 22 ） : 1900-1904.
5 Tan Huarong Tian Yuqing Yang Haihua and Chater Keith.
1997. In vivo transcription of two promoters, PTH4 and PTH270
involved in regulation of Streptomyces differentiation.
Science in China (Series C) , 40 (3): 246-250.
6 Tan Huarong Yang Haihua Tian Yuqing Wu Wei Carl Whatling
and Keith F Chater. 1998. The Streptomyces coelicolor
sporulation-specific σ whiG form ofRNA polymerase
transcribes a gene encoding a Prox-like protein that is
dispensable for sporulation. Gene , 212: 137-146.
7 Tian Yuqing Liu Gang Nie Liping Jia Junyong Tan Huarong
*. 1999. A novel gene--- samfR invovled in early stage of
Streptomyces ansochromogenes differentiation. Science in
China (Series C) . 42 （ 6 ） : 570-576.
8 Xiang Hua, Wei Wenzhong, Zhang Yiqing, Tan Huarong *.
2000. Cloning and expression of human glutathione
S-transferase gene in Lactococcus lacti s. Biomol. Eng . 16
(6): 207-209.
9 Jia Junyong, Li Wenli, Chen Wei, Nie Liping, Tan Huarong
*.2000. Cloning,sequencing and function of sanA , a gene
involved in nikkomycin biosynthesis of Streptomyces
ansochromogenes . Science in China (Series C) , 43(1): 30-38.
1 Yang Haihua, Tian Yuqing, Jia Junyong, Tan Huarong * .
2000. The function of a regulatory gene, scrX related to
differentiation in Streptomyces coelicolor . Science in China
(Series C) , 43(2): 157-168.
1 Nie Liping, Wang Yunxun, Jia Junyong, Tian Yuqing, Tan
Huarong * . 2000. Structure and function of sawB , a gene
involved in differentiation of Streptomyces ansochromogenes .
Science in China (Series C) , 43(4): 376-386.
1 Chen Wei, Zeng Hongmei, Tan Huarong *. 2000. Cloning,
sequencing and function of sanF involved in nikkomycin
biosynthesis in Streptomyces ansochromogenes . Current
Microbiol ., 41 （ 5 ） : 312-316.
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1 Li Wenli, Jia Junyong, Tan Huarong *. 2000. Cloning,
sequencing and function of sanB , a gene related to nikkomycin
biosynthesis of Streptomyces ansochromogenes . Chinese
Science Bulletin , 45 (23):2157-2162.
1 Nie Liping Tan Huarong *.2001.Molecular regulation of
development and differentiation in Streptomyces . Chinese
Science Bulletin , 46 (3):177-178.
1 Tan Huarong Tian Yuqing Yang Haihua et al..2002. A novel
Streptomyces gene, samR , with different effects on
differentiation of Streptomyces ansochromogenes and
Streptomyces coelicolor . Archives of Microbiology , 177 (3):
274-278.
1 Bao Q, Tian Y., Li W, Xu Z, Hu S, Dong W, Xue Y, Xu Y, Lai
X, Huang L, Dong X, Ma Y, Ling L, Tan H *, Chen R, Wang J, Yu
J, Yang H. 2002. A complete sequence of the T. tengcongensis
genome. Genome Res . 12(5); 689-700.
1 Zeng Hongmei, Tan Huarong *. 2002. Cloning and function
of sanQ: A gene involved in nikkomycin biosynthesis of
Streptomyces ansochromogenes . Current Microbiol ., 45(3):
175-179.
1 Zhang Jihui Ma Wenbo Tan Huarong * . 2002. Cloning,
expression and characterization of a gene encoding
nitroalkane-oxidizing enzyme from Streptomyces
ansochromogenes. Eur. J. Biochem. , 269 (24): 6302-6307.
1 He Xiuping,Zhang Borun* and Tan Huarong*. 2003.
Overexpression of a sterol C-24(28) reductase increases
ergosterol production in Saccharomyces Cerevisiae, Biotech
Lett.,25(10):773-778.
2 Xu Jianyong Liu Gang Tan Huarong* . 2003. sanC —a novel
gene involved in nikkomycin biosynthesis in Streptomyces
ansochromogenes . Letters in Applied Microbiology , 36:
234-238.
2 Xiang Hua Wei Wenzhong Tan Huarong* . 2003. Food-grade
expression of human glutathion S-transferase and Cu/Zn
superoxide dismutase in Lactococcus lactis . Biomolecular
Engineering , 20: 107-112.
2 Li Wenli and Tan Huarong* . 2003. Structure and function
of sanV : a gene involved in nikkomycin biosynthetic pathway
of Streptomyces ansochromogenes . Current Microbiolog,
46(6) : 403-407.
2 Wang Guojun Nie Liping Tan Huarong* . 2003. Cloning and
characterization of sanO , a gene involved in nikkomycin
biosynthesis in Streptomyces ansochromogenes . Lett. Appl.
Microbiol., 36: 452-457.
2 Li Wenli Liu Gang Tan Huarong* . 2003. Disruption of sabR
affects nikkomycin biosynthesis and morphogenesis in
Streptomyces ansochromogenes . Biotechnol Lett. 25 （ 18 ）：
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1491-1497 。
2 Li Yun Xiang Hua Liu Jingfang Zhou Meixian Tan Huarong.
2003. Purification and biological characterization of halocin
C8, a novel peptide antibiotic from halobacterium strain
AS7092. Extremophiles . 7: 401-407.
2 Wang Guojun Tan Huarong* . 2004. Enhanced production of
nikkomycin X by over-expression of SanO, a non-ribosomal
peptide synthetase in Streptomyces ansochromogenes .
Biotechnol. Lett., 26(3): 229-233.
2 Zhou Meixian Xiang Hua Sun Chaomin Li Yun Liu Jingfang Tan
Huarong . 2004. Complete sequence and molecular
characterization of pNB101, a rolling-circle replicating
plasmid from the haloalkaliphilic archaeon Natronobacterium
sp . Strain AS7091. Extremophiles , 8: 91-98.
2 Li Yirong Zeng Hongmei Tan Huarong* . 2004. Cloning,
Function and expression of sansS : A gene essential for
nikkomycin biosynthesis of Streptomyces ansochromogenes .
Current Microbiology, 49: 128-132 .
2 Liu Gang Tian Yuqing Yang Haihua Tan Huarong*.2005. A
pathway-specific transcriptional regulatory gene for
nikkomycin biosynthesis in Streptomyces ansochromogenes that
also influences colony development. Molecular
Microbiology,55(6):1855-1866.
3 Li Yirong Ling Hongbo Li Wenli Tan Huarong*.2005.
Improvement of nikkomycin production by enhanced copy of sanU
and sanV in Streptomyces ansochromogenes and characterization
of a novel glutamate mutase encoded by sanU and sanV. Metabolic
Engineering.7:165-173.
Patents
ZL 01142016.2. An engineered strain producing nikkomycin Z and its application.
Huarong Tan and Hongmei Zeng.
Laboratory Staff
Dr. Gang Liu
Associate Professor
Liug@im.ac.cn
Dr. Haihua Yang
Associate Professor
Yanghh@im.ac.cn
Tian yuqing
Assistant Professor
Tianyq@im.ac.cn
Students
Yirong Li，2001-2005
Guoqing Niu，
2002-2006
Chenrong Lin
2002-2005
Lianghui Jia，2003-2006
Hongbo Ling，
2003-2006
Zhoujie Xie，
2002-2007
Kun Hu，2002-2007
Yanhua Li， 2004-2007
Yuanyuan Pan，
2005-2008
Guohua Zhang，
2005-2008
Yuling Gai，2002-2005
Linqi Wang，2003-2006
Xiaohua Yan，2003-2006
Rui Li，2004-2009
Yue Zhang，2004-2007
Liang Liang，2004-2007