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孙宇辉

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孙宇辉，理学博士、楚天学者特聘教授、武汉大学药学院教授、博士生导师，药学院院长助理。从事天然产物生物合成的分子遗传学、生物化学及组合生物合成研究。曾获得国家自然科学二等奖等奖项。

研究领域:微生物来源天然产物生物合成的分子遗传学、生物化学及合成生物学;承担课题10余项。

对具有重要基础和应用价值的活性天然产物的生物合成机制及其分子改造进行了多年的探索和积累，在权威学术期刊，如《Nature Chemical Biology》、 《Angewandte Chemie International Edition》、《Chemistry & Biology》等发表研究论文二十余篇。此外，合作编译国外专业教材一部，获国家发明专利两项和多项国家、省(部)级奖励。

基本信息

人物说明----武汉大学药学院教授、博士生导师

国 籍 ---- 中国

职 业 ---- 教育科研工作者

主要成就----国家自然科学二等奖等奖项

毕业院校----江西农业大学，上海交通大学

职 称 ---- 博士生导师

学习简历

1988.9―1992.7 江西农业大学 攻读植物遗传育种专业学士学位

1997.9―2001.3 华中农业大学 攻读生物化学与分子生物学专业硕士学位

2001.3―2004.3 上海交通大学 攻读生物化学与分子生物学专业博士学位

工作简历

1992.7―1998.9 江西农业大学 生物技术研究开发中心 研究实习员(初级)

1998.9―2002.10 江西农业大学 生物技术研究开发中心 助理研究员(中级)

2002.10―2006.11 江西农业大学 生物工程系 副教授

2006.11―2009.11 江西农业大学 生物工程与技术学院 教授

2005.1―2010.5 剑桥大学 生物化学系 Royal Society China Fellow，Senior Research Associate

2010.5― 武汉大学药学院 楚天学者特聘教授

业绩概要

对具有重要基础和应用价值的活性天然产物的生物合成机制及其分子改造进行了多年广泛而深入的探索和积累，在国外权威学术期刊，如"Nature﹒Chemical Biology"、"Chemistry & Biology"、"ChemBioChem"、"Journal of Bacteriology"、"Microbiology"、"Applied Microbiology and Biotechnology"、"Archives of Microbiology"、"FEMS Microbiology Letters"共发表研究论文13篇，分别在第13届(2005)和第15届(2009)International Symposium on the Biology of Actinomycetes，第4届Chemistry and Biology of Natural Products(2008)，第2届Natural Products Conference(2009)国际专业会议上受邀进行大会报告。此外，合作编译国外专业教材一本，获国家发明专利2项并荣获多项国家和省(部)级奖励。

获奖情况

国家自然科学二等奖(2008)

江西省自然科学二等奖(2007)

全国优秀博士论文提名(2007)

江西省高校科技成果奖(2006)

上海市研究生优秀成果(学位论文)奖(2006)

上海市科技进步一等奖(2004)

研究领域

天然产物生物合成的分子遗传学、生物化学及组合生物合成。基于微生物的活性天然产物生物合成途径的发现与开发。针对性地从微生物中寻找具有重要基础和应用价值的活性天然产物，一方面，以参与天然产物生物合成途径相关基因与蛋白的结构与功能为主要内容，探索其生物合成的酶促催化机制，从分子遗传学和生物化学的角度阐明结构新颖、活性特异的天然产物的生物合成机理，在分子水平上回答其生物合成的一些重要问题，并进而为蛋白分子和酶促产物的改造提供结构基础和理论依据，为新药物的组合生物合成提供精确的"分子装配线路图"。另一方面通过对新的酶促反应和代谢途径的发现和功能分析，对这些酶促代谢途径进行改进和优化，在此基础上创造出"非天然"的天然产物分子。同时，采用分子定向进化等技术，获得更高效率、更好稳定性和使用性的新型酶分子，解析酶分子的催化动力学及酶蛋白的晶体结构和催化的分子机制，使之能更为有的放矢地利用天然产物生物合成途径来主动性地高产或创新微生物药物。

承担课题

● 国家自然科学基金面上项目(2015-2018，2013-2016)

● 微生物代谢国家重点实验室(上海交通大学)开放课题(2015-2017)

● 国家重点基础研究发展计划(973)子课题(2012-2016)

● 国家高技术研究发展计划(863计划) 子课题(2012-2015)

● 国家"重大新药创制"科技重大专项子课题(2011-2013)

● 教育部高等学校博士点专项科研基金(博导类)(2012-2014)

● 教育部海外名师项目(2012-2017)

● 湖北省研究与开发计划项目(2012-2014)

● 武汉大学医学部协同创新项目(2013-2015)

● 武汉大学自主科研项目(2011-2013)

发表的学术论文

(*:通讯作者，#:第一作者)

● Yunkun Liu, Weixin Tao, Shishi Wen, Zhengyuan Li, Anna Yang, Zixin Deng and Yuhui Sun* (2015) In vitro CRISPR/Cas9 system for efficient targeted DNA editing. mBio. 6:e 01714-15.

● Weixin Tao, Marie E. Yurkovich, Shishi Wen, Karen E. Lebe, Markiyan Samborskyy, Yuanzhen Liu, Anna Yang, Yunkun Liu, Yingchen Ju, Zixin Deng, Manuela Tosin, Yuhui Sun* and Peter F. Leadlay* (2015) A genomics-led approach to deciphering the mechanism of thiotetronate antibiotic biosynthesis. Chemical Science. (In press)

● Hu Zeng, Shishi Wen, Wei Xu, Zhaoren He, Guifa Zhai, Yunkun Liu, Zixin Deng and Yuhui Sun* (2015) Highly efficient editing of the actinorhodin polyketide chain length factor gene in Streptomyces coelicolor M145 using CRISPR/Cas9-CodA(sm) combined system. Applied Microbiology and Biotechnology. (In press)

● Chuan Huang, Fanglu Huang, Eileen Moison, Junhong Guo, Xinyun Jian, Xiaobo Duan, Zixin Deng, Peter F. Leadlay* and Yuhui Sun* (2015) Delineating the biosynthesis of gentamicin X2, the common precursor of the gentamicin C antibiotic complex. Chemistry & Biology 22:251-261.

● Yuhui Sun* (2014) A carbonate architect emerges. Nature Chemical Biology 10:486-487. (Invited Comments)

● Junhong Guo, Fanglu Huang, Chuan Huang, Xiaobo Duan, Xinyun Jian, Finian Leeper, Zixin Deng, Peter F. Leadlay* and Yuhui Sun* (2014) Specificity and promiscuity at the branch point in gentamicin biosynthesis. Chemistry & Biology 21:608-618.

● Yanling Ma, Wei Xu, Jun Zhang, Sihong Zhang, Kui Hong, Zixin Deng and Yuhui Sun* (2014) Nitrilase superfamily aryl acylamidase from the halotolerant mangrove Streptomyces sp. 211726. Applied Microbiology and Biotechnology 19:8583-8590.

● Weixin Tao, Manghong Zhu, Zixin Deng and Yuhui Sun* (2013) Biosynthesis of tetronate antibiotics: A growing family of natural products with broad biological activities. Science China Chemistry 56:1364-1371. (Invited Review)

● Chompoonik Kanchanabanca, Weixin Tao, Hui Hong, Yajing Liu, Frank Hahn, Markiyan Samborskyy, Zixin Deng, Yuhui Sun* and Peter F. Leadlay* (2013) Unusual acetylation-elimination in the formation of tetronate antibiotics. Angewandte Chemie International Edition 52:5785-5788.

● MarieE. Yurkovich, PetrosA. Tyrakis, Hui Hong, Yuhui Sun, Markiyan Samborskyy, Kohei Kamiyaand PeterF. Leadlay* (2012) A late-stage intermediate in salinomycin biosynthesis is revealed by specific mutation in the biosynthetic gene cluster. ChemBioChem 13:66-71.

● Jeroen S. Dickschat, Olivia Vergnolle, Hui Hong, Stephen Garner, Susanna R. Bidgood, Hannah C. Dooley, Zixin Deng, Peter F. Leadlay* and Yuhui Sun* (2011) An additional dehydratase-like activity is required for lankacidin antibiotic biosynthesis. ChemBioChem 12:2408-2412.

注:本论文被 "Nature Chemical Biology, 2011,7(12):856"作为"研究亮点(Research Highlights)"推荐。

● Yuhui Sun*, Frank Hahn, Yuliya Demydchuk, James Chettle, Manuela Tosin, Hiroyuki Osada and Peter F. Leadlay* (2010) In vitro reconstruction of tetronate RK-682 biosynthesis. Nature Chemical Biology 6:99-101.

注:本论文被英国Faculty of 1000收录(http://f1000.com/)并获专家点评。

● Yunlong He, Yuhui Sun, Tiangang Liu, Xiufen Zhou, Linquan Bai and Zixin Deng* (2010) Cloning of separate meilingmycin biosynthesis gene clusters by use of acyltransferase-ketoreductase didomain PCR amplification. Applied and Environmental Microbiology 76:3283-3292.

● Yuhui Sun, Xinyi He, Jingdan Liang, Xiufen Zhou and Zixin Deng* (2009) Analysis of functions in plasmid pHZ1358 influencing its genetic and structural stability in Streptomyces lividans 1326. Applied Microbiology and Biotechnology 82:303-310.

● David H. Kwan, Yuhui Sun, Frank Schulz, Hui Hong, Bojana Popovic, Joalice C.C. Sim-Stark, Stephen F. Haydock and Peter F. Leadlay* (2008) Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases. Chemistry & Biology 15:1231-1240.

● Yuliya Demydchuk, Yuhui Sun, Hui Hong, James Staunton, Jonathan B. Spencer and Peter F. Leadlay* (2008) Analysis of the tetronomycin gene cluster: insights into the biosynthesis of a polyether tetronate antibiotic. ChemBioChem 9:1136-1145.

● Yuhui Sun, Hui Hong, Fraser Gillies, Jonathan B. Spencer and Peter F. Leadlay* (2008) Glyceryl-S-acyl carrier protein as an intermediate in the biosynthesis of tetronate antibiotics. ChemBioChem 9:150-156.

● Barbara M. Harvey, Tatiana Mironenko, Yuhui Sun, Hui Hong, Zixin Deng, Peter F. Leadlay, Kira J. Weissman and Stephen F. Haydock* (2007) Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137. Chemistry & Biology 14:703-714.

● Yuhui Sun, Hui Hong, Markiyan Samborskyy, Tatiana Mironenko, Peter F. Leadlay and Stephen F. Haydock* (2006) Organization of the biosynthetic gene cluster in Streptomyces sp. DSM 4137 for the novel neuroprotectant polyketide meridamycin. Microbiology 152:3507-3515.

● Tiangang Liu, Delin You, Chiara Valenzano, Yuhui Sun, Jialiang Li, Qing Yu, Xiufen Zhou, David E. Cane and Zixin Deng* (2006) Identification of NanE as the thioesterase for polyether chain release in nanchangmycin biosynthesis. Chemistry & Biology 13:945-955.

● Yuhui Sun, Xiufen Zhou, Hui Dong, Guoquan Tu, Min Wang, Bofei Wang and Zixin Deng* (2003) A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin. Chemistry & Biology 10:431-441.

● Yuhui Sun, Xiufen Zhou, Guoquan Tu and Zixin Deng* (2003) Identification of a gene cluster encoding meilingmycin biosynthesis among multiple polyketide synthase contigs isolated from Streptomyces nanchangensis NS3226. Archives of Microbiology 180:101-107.

● Yuhui Sun, Xiufen Zhou, Jun Liu, Kai Bao, Guiming Zhang, Guoquan Tu, Tobias Kieser and Zixin Deng* (2002) 'Streptomyces nanchangensis', a producer of the insecticidal polyether antibiotic nanchangmycin and the antiparasitic macrolide meilingmycin, contains multiple polyketide gene clusters. Microbiology 148:361-371.

● Xiuhua Pang, Yuhui Sun, Liu Jun, Xiufen Zhou and Zixin Deng* (2002) A linear plasmid temperature-sensitive for replication in Streptomyces hygroscopicus 10-22. FEMS Microbiology Letters 208:25-28.

● Xiuhua Pang, Xiufen Zhou, Yuhui Sun and Zixin Deng* (2002) Physical map of the linear chromosome of Streptomyces hygroscopicus 10-22 deduced by analysis of overlapping large chromosomal deletions. Journal of Bacteriology 184:1958-1965.