Natural Products Biosynthesis and DNA S Modification
Dr. Delin: You received his B.S. degree in 1991 from Changchun University of Technology and his Ph.D. degree in 2001 from Jilin University. His Ph.D. mentor was Professor Tongshu Yang. After a two-year postdoctoral fellowship at Peking University with Professor Ming Luo, he began his research career as an associate professor at Shanghai Jiao Tong University in 2003. From 2010 to 2011 he worked with Professor Peter C. Dedon as a research scientist at Massachusetts Institute of Technology on biochemical pathways of DNA phosphorothioation. Dr. You’s interests include natural products biosynthesis and phosphorothioate modifications of DNA. Over the past several years, he has focused his research on investigating biosynthetic pathways and enzymatic reaction mechanisms of polyketide antibiotics, such as Xantholipin, Chlortetracycline, Piericidin, Agri-Antibiotic 120 (Anisomycin and Tetramycin) and Candicidin, as well as biochemical pathways and biological functions of DNA phosphorothioation. His research was supported by the National Science Foundation of China, the Ministry of Science and Technology (973 and 863 Programs), China Ocean Mineral Resources R & D Association and the Shanghai Municipal Council of Science and Technology.
1. Phosphorothioate modifications of DNA
Figure 1 Mutational analysis of the dpt gene cluster of S. enterica serovar Cerro 87. (Xu, et al. Nucleic Acids Res. 2010)
2. Natural products biosynthesis
Figure 3 Elucidation of Piericidin A1 biosynthetic locus revealed a thioesterase-dependent mechanism of α-pyridone ring formation. (Liu, et al. Chem Biol. 2012)
1998.09-2001.07 Ph. D. in Biochemistry and Molecular Biology, Jilin University
1995.09-1998.07 M. Sc. in Biochemistry and Molecular Biology, Jilin University
1987.09-1991.07 B.S. in Chemical engineering, Changchun University of Technology
2003.10- Associate Professor, Shanghai Jiao Tong University
2010.08-2011.08 Senior Visiting Scholar, Department of Biological Engineering, Massachusetts Institute of Technology
2001.10-2003.10 Postdoctoral Fellow, College of Life Sciences, Peking University
1991.11-1998.10 Engineer, State Key Laboratory of Enzyme Engineering Jilin University
Selected recent Publications:
1. Zhang C, Kong L, Liu Q, Lei X, Zhu T, Yin J, Lin B, Deng Z, You D*. In vitro characterization of echinomycin biosynthesis: formation and hydroxylation of L-tryptophanyl-S-enzyme and oxidation of (2S,3S) β-hydroxytryptophan. PLoS One 2013, 8 (2): e56772.
2. Lei X, Kong L, Zhang C, Liu Q, Yao F, Zhang W, Deng Z, You D*. In vivo investigation of the substrate recognition capability and activity affecting amino acid residues of glycosyltransferase FscMI in biosynthesis of candicidin. Mol BioSyst. 2013, 9 (3): 422-430.
3. Cao B, Yao F, Zheng X, Cui D, Shao Y, Zhu C, Deng Z, You D*. Genome mining of the biosynthetic gene cluster of the polyene macrolide antibiotic tetramycin and characterization of a P450 monooxygenase involved in the hydroxylation of the tetramycin B polyol segment. ChemBioChem. 2012, 13(15):2234-42
4. Zhang W, Wang L, Kong L, Wang T, Chu Y, Deng Z, You D*. Unveiling the post-PKS redox tailoring steps in biosynthesis of the type II polyketide antitumor antibiotic xantholipin. Chem Biol. 2012, 19(3):422-32.
5. Liu Q, Yao F, Chooi Y, Kang Q, Xu W, Li Y, Shao Y, Shi Y, Deng Z, Tang Y*, You D*. Elucidation of piericidin A1 biosynthetic locus revealed a thioesterase-dependent mechanism of α-pyridone ring formation. Chem Biol. 2012, 19(2):243-53.
6. Wang T, Bai L, Zhu D, Lei X, Liu G, Deng Z, You D*. Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes. Enzyme Microb.Tech. 2012, 50: 5-9.
7. Xu T, Yao F, Zhou X, Deng Z*, You D*. A novel host-specific restriction system associated with DNA backbone S-modification in Salmonella. Nucleic Acids Research. 2010, 38(20): 7133-41.
8. Yao F, Xu T, Zhou X, Deng Z*, You D*. Functional analysis of spfD gene involved in DNA phosphorothioation in Pseudomonas fluorescens Pf0-1. FEBS Lett. 2009, 583(4):729-33.
9. Chen W, Huang T, He X, Meng Q, You D, Bai L, Li J, Wu M, Li R, Xie Z, Zhou H, Zhou X, Tan H, Deng Z*. Characterization of the polyoxin biosynthetic gene cluster from Streptomyces cacaoi and engineered production of polyoxin H. J Biol Chem. 2009, 284(16): 10627-38.
10. Xu T, Liang J, Chen S, Wang L, He X, You D, Wang Z, Li A, Xu Z, Zhou X, Deng Z*. DNA phosphorothioation in Streptomyces lividans: mutational analysis of the dnd locus. BMC Microbiol. 2009, 9: 41.
11. Zhou Y, Meng Q, You D, Li J, Chen S, Ding D, Zhou X, Zhou H, Bai L, Deng Z*. Selective removal of aberrant extender units by a type II thioesterase for efficient FR-008/candicidin biosynthesis in Streptomyces sp. strain FR-008. Appl Environ Microbiol. 2008, 74(23):7235-42.
12. You D*, Xu T, Yao F, Zhou X, Deng Z*. Direct evidence that ThiI is an ATP pyrophosphatase for the adenylation of uridine in 4-thiouridine biosynthesis. ChemBioChem 2008, 9(12):1879-82.
13. Wang L, Chen S, Xu T, Taghizadeh K, Wishnok JS, Zhou X, You D, Deng Z*, Dedon PC*. Phosphorothioation of DNA in bacteria by dnd genes. Nat Chem Biol. 2007, 3(11): 709-10.
14. You D, Wang L, Yao F, Zhou X, Deng Z*. A novel DNA modification by sulfur: DndA is a NifS-like cysteine desulfurase capable of assembling DndC as an iron-sulfur cluster protein in Streptomyces lividans. Biochemistry. 2007, 46(20):6126-33.
15. Liu T, You D, Valenzano C, Sun Y, Li J, Yu Q, Zhou X, Cane DE, Deng Z*. Identification of NanE as the thioesterase for polyether chain release in nanchangmycin biosynthesis. Chem Biol. 2006, 13(9):945-55.
16. Wang L, Chen S, Xiao X, Huang X, You D, Zhou X, Deng Z*. arsRBOCT arsenic resistance system encoded by linear plasmid pHZ227 in Streptomyces sp. strain FR-008. Appl Environ Microbiol. 2006, 72(5):3738-42.
1. You D. Principles of enzyme engineering. Beijing: science press, 2011.
4. You D, Liu Q, Sun D, Wu J, Shi Y, Deng Z. Piericidin A1 biosynthetic gene cluster. China patent 201110063924.2
3. You D, Wang T, Zhu D, Bai L, Deng Z. A metabolic engineering approach for enhanced antibiotic production in Streptomyce. China patent 201110054035.X
2. You D, Zhang W, Deng Z, Chu Y, Wang L, Zhao Z. Biosynthesis gene cluster of Xantholipin. China patent 201010251262.7
1. Deng Z, Wang L, Chen S, You D, Zhou X, Xiao X, Huang X. An arsenic resistance gene cluster in linear plasmid of Streptomyces sp. strain FR-008. China patent ZL20051003098
2012 Meiji Life Sciences Award
2012 Shanghai Pujiang Program
2008 SMC Excell Young Faculty Award
2007 Global Science Top 10
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