由德林 的个人介绍页
由德林
由德林
教授
...
mml.sjtu.edu.cn
62932943

个人简历

2001年于吉林大学获生物化学与分子生物学专业博士学位;2001-2003年在北京大学生命科学学院做博士后研究;2003年于上海交通大学生命科学技术学院工作,聘为副教授,博士生导师,2014年被聘为教授;2010-2011年在麻省理工学院进行合作研究。研究领域涉及微生物天然产物生物合成和DNA大分子磷硫酰化修饰。作为项目负责人先后主持国家自然科学基金项目5项、国家高技术研究发展计划项目(863计划) 3项、国家重点基础研究发展计划项目(973计划)子课题1项和上海市自然科学基金项目1项。相关研究成果发表在Chemistry & Biology、Nucleic Acids Research、Metabolic Engineering、 Biochemistry和Nature Chemical Biology等。2008年入选首届上海交通大学晨星青年学者奖励计划(A类);2012年获得明治生命科学奖(科学奖),入选上海市浦江人才计划。

研究方向

1. DNA磷硫酰化修饰
在DNA 骨架上发现DNA磷硫酰化生理修饰结构基础上,以表观遗传学领域的新技术和新方法,研究新型表观遗传修饰-DNA磷硫酰化的生物化学途径和全基因组上的修饰序列特征,并深入探索这种新型表观遗传修饰在细胞防卫、基因表达调控等方面潜在的生理功能。
2. 微生物天然产物的生物合成
以具有新颖结构、独特生理活性的微生物次级代谢产物为研究对象,综合运用生物化学、分子遗传学和化学生物学等手段,开展微生物次级代谢产物的分离鉴定、生物合成基因簇的克隆、生物合成途径和调控机制及生物活性与功能的研究,并在此基础上开展活性天然产物的结构修饰和组合生物合成改造。目前集中在微生物天然产物xantholipin、piericidin、chlortetracycline、agri-antibiotic 120(anisomycin 和tetramycin)和candicidin的生物合成途径和酶反应机制研究。

发表论文

发表的主要论文(*通讯作者):
1. Cheng Q, Cao B, Yao F, Li J, Deng Z, You D*. Regulation of DNA phosphorothioate modifications by the transcriptional regulator DptB in Salmonella. Molecular Microbiology 2015, doi: 10.1111/mmi.13096.
2. Cao B, Zheng X, Cheng Q, Yao F, Zheng T, Babu IR, Zhou H, Dedon PC, You D*. In vitro analysis of phosphorothioate modification of DNA reveals substrate recognition by a multiprotein complex. Scientific Reports 2015, doi: 10.1038/srep12513.
3. Cao B, Cheng Q, Gu C, Yao F, DeMott MS, Zheng X, Deng Z, Dedon PC, You D*. Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella. Molecular Microbiology 2014, 93(4):776-785.
4. Cao B, Chen C, DeMott MS, Cheng Q, Clark TA, Xiong X, Zheng X, Butty V, Levine SS, Yuan G, Boitano M, Luong K, Song Y, Zhou X, Deng Z, Turner SW, Korlach J, You D*, Wang L*, Chen S*, Dedon PC. Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences. Nature Communications 2014, 5: 3951.
5. Zhu T, Cheng X, Liu Y, Deng Z, You D*. Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens. Metabolic Engineering 2013, 19:69-78.
6. 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.
7. 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. Molecular BioSystems 2013, 9 (3): 422-430.
8. 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.
9. 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. Chemistry & Biology 2012, 19(3):422-32. (Cell Press journals)
10. 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. Chemistry & Biology 2012, 19(2):243-53. (Cell Press journals)
11. 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 and Microbial Technology 2012, 50: 5-9. (Comments by Faculty of 1000)
12. 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. (selected as feature article)
13. 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 Letters 2009, 583(4):729-33.
14. 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. The Journal Biological Chemistry 2009, 284(16): 10627-38.
15. 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 Microbiology 2009, 9: 41.
16. 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. Applied Environmental Microbiology 2008, 74(23):7235-42.
17. 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.
18. 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. Nature Chemical Biology 2007, 3(11): 709-10. (Comments by Nat Chem Biol, C&EN, Nature China)
19. Chen Q, You D, Liang Y, Su X, Gu X, Luo M, Zheng X*. Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design. FEBS Journal 2007, 274(17):4408-15.
20. 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.
21. 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. Chemistry & Biology 2006, 13(9):945-55. (Cell Press journals)
22. 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. Applied Environmental Microbiology 2006, 72(5):3738-42.

研究成果

著作:
1. 《酶工程原理》, 由德林主编, 北京: 科学出版社, 2011.

发明专利:
5. 四霉素的生物合成基因簇, 项目负责人, 申请号: 201110365125.0
4. 杀粉蝶菌素A1生物合成基因簇, 项目负责人, 申请号: 201110063924.2
3. 提高链霉菌抗生素产量的方法及其质粒, 项目负责人,申请号:201110054035.X
2. 黄脂菌素的生物合成基因簇, 项目负责人, 申请号:201010251262.7
1. 链霉菌线性质粒中抗砷基因簇, ZL20051003098