Huarong Tan
Ph.D., Professor

 

Institute of Microbiology
Chinese Academy of Sciences
Tel: 86-10-64807461
E-mail: tanhr@im.ac.cn

Research Area
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 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.

10

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.

11

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.

12

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.

13

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.

14

Nie Liping Tan Huarong *.2001.Molecular regulation of development and differentiation in Streptomyces . Chinese Science Bulletin , 46 (3):177-178.

15

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.

16

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.

17

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.

18

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.

19

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.

20

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.

21

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.

22

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.

23

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.

24

Li Wenli Liu Gang Tan Huarong* . 2003. Disruption of sabR affects nikkomycin biosynthesis and morphogenesis in Streptomyces ansochromogenes . Biotechnol Lett. 25 ( 18 ): 1491-1497 。

25

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.

26

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.

27

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.

28

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 .

29

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.

30

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