Based on Genomics, functional genomics and comparative genomics information, special metabolic processes of microorganisms and the related genetic and biochemical/physiological molecular mechanisms of regulation under different environmental conditions are systematically studied. Metabolic regulation models are being developed based on the knowledge of characterizing signal transduction systems and transcription factors with respect to gene transcription, protein structure and function modification and interaction, as well as the biological small molecules.

Principal Investigator: Dr. Guo-Ping Zhao, Professor, Academician. Email: gpzhao@sibs.ac.cn
Advisors: Dr. Rui-Shen Jiao (Juishen Chiao), Professor; Dr. Xiao-Kui Guo, Professor. Email: microbiology@sjtu.edu.cn
Staff: Chen Li, Research Intern; Jun-Wei Yang, Research Intern; Chen-Hao Zhang, Research Intern; Hui Ma, Research Intern
Graduate Students: Jun Ma; Qing Zhang; Zhi-Hui Shao; Xiao-Dong Shang; Jin Wang; Nan-Qiu Peng; Yun-Yi Zhang; Ying Wang; Zi-Long Zhang; Wei Zhao; Han Yan; Wei Lin
Graduated Student: Ying Zou, 2003 (PhD)
Visiting Scholars: Dr. Xiao-Ming Ding, Lecturer (Fudan University); Dr. Yu-Feng Yao, Associate Professor (Shanghai Jiao Tong University)

Amycolatopsis mediterranei U32 GlnR Regulates the Transcription of glnA and ald, Basic Genes for Ammonium Assimilation Apparently via Specific Binding to a Novel GlnR Box
Ammonium is assimilated in Amycolatopsis mediterranei U32 mainly through alanine dehydrogenase (AlaDH) or GS/GOGAT pathways depending on the availability of nitrogen sources. Upon nitrogen deprivation, GlnR both activates the transcription of the GS encoding gene glnA and represses the AlaDH encoding gene ald. Comparing the GlnR protected cis-elements in their promoters, a characteristic 16-bp sequence designated GlnR Box, composed of two 8-bp half boxes (Box1 and Box2), was deduced and proven essential for GlnR binding. The GlnR Box1 and Box2 were continuous in glnA promoter but departed by 76 base in ald promoter, where DNA looping was observed via AFM with GlnR bound to both GlnR Box1 and Box2. With its major transcription initiation site (aldP2) situated in the middle of GlnR Box2, the transcription initiated from aldP2 is proposed to be blocked by the bound GlnR, which likely accounts for the in vivo GlnR mediated stringent repression. Similar GlnR Box was found in Streptomyces coelicolor, while the mechanism for GlnR Box mediated GlnR regulation is still under tested.

Publications:

1. Xu Z, et al, Zhao GP*, Chen H*. (2008) Genome Biology of Actinobacillus pleuropneumoniae JL03, an Isolate of Serotype 3 Prevalent in China. PLoS ONE 3: e1450.

2. Li M, et al, Zhao GP*, Nicholson JK*, Li LJ * and Zhao LP*. (2008) Symbiotic gut microbes modulate human metabolic phenotypes. Proc. Natl. Acad. Sci. USA. 105: 2117-2122.

3. Zheng H, et al, Zhao G*, Zhang Y*. (2008) Genetic basis of virulence attenuation revealed by comparative genomic analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv. PLoS ONE. 3: e2375.

4. Jun MA, et al, Zhao GP* and Ding JP*. (2008) Molecular basis of the substrate specificity and the catalytic mechanism of citramalate synthase from Leptospira interrogans. Biochem. J. 415: 45-56.

5. Zhang L, Ou XJ, Zhao GP* and Ding XM*. (2008) Highly efficient in vitro site-specific recombination system based on Streptomyces phage BT1 integrase. J. Bacteriol. 190: 6392-6397.
   (* corresponding author)

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