孫宇輝是理學博士、楚天學者特聘教授、武漢大學藥學院教授、博士生導師藥學院院長助理。從事天然產物生物合成的分子遺傳學、生物化學及組合生物合成研究。曾獲得國家自然科學二等獎等獎項。
研究領域:微生物來源天然產物生物合成的分子遺傳學、生物化學及合成生物學;承擔課題10余項。
對具有重要基礎和應用價值的活性天然產物的生物合成機制及其分子改造進行了多年的探索和積累,在權威學術期刊,如《Nature Chemical Biology》、 《Angewandte Chemie International Edition》、《Chemistry & Biology》等發表研究論文二十余篇。此外,合作編譯國外專業教材一部,獲國家發明專利兩項和多項國家、省(部)級獎勵。
學習簡歷
1988.9―1992.7 江西農業大學 攻讀植物遺傳育種專業學士
1997.9―2001.3華中農業大學 攻讀生物化學與分子生物學專業碩士學位
2001.3―2004.3 上海交通大學 攻讀生物化學與分子生物學專業博士學位
工作簡歷
1992.7―1998.9 江西農業大學 生物技術研究開發中心 研究實習員(初級)
1998.9―2002.10 江西農業大學 生物技術研究開發中心 助理研究員(中級)
2002.10―2006.11 江西農業大學 生物工程系 副教授
2006.11―2009.11 江西農業大學 生物工程與技術學院 教授
2005.1―2010.5 劍橋大學 生物化學系 Royal Society China Fellow,Senior Research Associate
業績概要
對具有重要基礎和應用價值的活性天然產物的生物合成機制及其分子改造進行了多年廣泛而深入的探索和積累,在國外權威學術期刊,如“Nature﹒Chemical Biology”、“化學 & Biology”、“ChemBioChem”、“Journal of 細菌學”、“Microbiology”、“Applied Microbiology and Biotechnology”、“Archives of Microbiology”、“FEMS Microbiology Letters”共發表研究論文13篇,分別在第13屆(2005)和第15屆(2009)International Symposium on the Biology of Actinomycetes,第4屆化學 and Biology of Natural Products(2008),第2屆Natural Products Conference(2009)國際專業會議上受邀進行大會報告。此外,合作編譯國外專業教材一本,獲國家發明專利2項并榮獲多項國家和省(部)級獎勵。
獲獎情況
國家自然科學二等獎(2008)
江西省自然科學二等獎(2007)
全國優秀博士論文提名(2007)
江西省高校科技成果獎(2006)
上海市研究生優秀成果(學位論文)獎(2006)
上海市科技進步一等獎(2004)
研究領域
天然產物生物合成的分子遺傳學、生物化學及組合生物合成。基于微生物的活性天然產物生物合成途徑的發現與開發。針對性地從微生物中尋找具有重要基礎和應用價值的活性天然產物,一方面,以參與天然產物生物合成途徑相關基因與蛋白的結構與功能為主要內容,探索其生物合成的酶促催化機制,從分子遺傳學和生物化學的角度闡明結構新穎、活性特異的天然產物的生物合成機理,在分子水平上回答其生物合成的一些重要問題,并進而為蛋白分子和酶促產物的改造提供結構基礎和理論依據,為新藥物的組合生物合成提供精確的“分子裝配線路圖”。另一方面通過對新的酶促反應和代謝途徑的發現和功能分析,對這些酶促代謝途徑進行改進和優化,在此基礎上創造出“非天然”的天然產物分子。同時,采用分子定向進化等技術,獲得更高效率、更好穩定性和使用性的新型酶分子,解析酶分子的催化動力學及酶蛋白的晶體結構和催化的分子機制,使之能更為有的放矢地利用天然產物生物合成途徑來主動性地高產或創新微生物藥物。
承擔課題
● 國家自然科學基金面上項目(2015-2018,2013-2016)
● 微生物代謝國家重點實驗室(上海交通大學)開放課題(2015-2017)
● 國家重點基礎研究發展計劃(973)子課題(2012-2016)
● 國家高技術研究發展計劃(863計劃) 子課題(2012-2015)
● 國家“重大新藥創制”科技重大專項子課題(2011-2013)
● 教育部高等學校博士點專項科研基金(博導類)(2012-2014)
● 教育部海外名師項目(2012-2017)
● 湖北省研究與開發計劃項目(2012-2014)
● 武漢大學醫學部協同創新項目(2013-2015)
● 武漢大學自主科研項目(2011-2013)
發表學術論文
(*:通訊作者,#:第一作者)
● Yunkun Liu, 微信 Tao, Shishi Wen, Zhengyuan Li, Anna Yang, Zixin Deng andYuhui Sun* (2015)In vitro CRISPR/Cas9 system for efficient targeted 脫氧核糖核酸 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 andYuhui Sun* (2015) Highly efficient editing of the actinorhodin polyketide chain length factor gene inStreptomyces 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* andYuhui Sun* (2015) Delineating the biosynthesis of gentamicin X2, the common precursor of the gentamicin C antibiotic complex.化學 & Biology22:251-261.
●Yuhui Sun* (2014) A carbonate architect emerges.Nature Chemical Biology10:486-487. (Invited Comments)
● Junhong Guo, Fanglu Huang, Chuan Huang, Xiaobo Duan, Xinyun Jian, Finian Leeper, Zixin Deng, Peter F. Leadlay* andYuhui Sun* (2014) Specificity and promiscuity at the branch point in gentamicin biosynthesis.化學 & Biology21:608-618.
● Yanling Ma, Wei Xu, Jun Zhang, Sihong Zhang, Kui Hong, Zixin Deng andYuhui Sun* (2014) Nitrilase 總科 aryl acylamidase from the halotolerant mangroveStreptomyces sp. 211726.Applied Microbiology and Biotechnology 19:8583-8590.
● Weixin Tao, Manghong Zhu, Zixin Deng andYuhui Sun* (2013) Biosynthesis of tetronate antibiotics: A growing family of natural products with broad biological activities.Science China 化學 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.ChemBioChem13:66-71.
● Jeroen S. Dickschat, Olivia Vergnolle, Hui Hong, Stephen Garner, Susanna R. Bidgood, Hannah C. Dooley, Zixin Deng, Peter F. Leadlay* andYuhui Sun* (2011) An additional dehydratase-like activity is required for lankacidin antibiotic biosynthesis.ChemBioChem 12:2408-2412.
注:本論文被“Nature Chemical Biology, 2011,7(12):856”作為“研究亮點(Research Highlights)”推薦。
●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:本論文被英國Faculty of 1000收錄(http://f1000.com/)并獲專家點評。
● 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 Microbiology76:3283-3292.
●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鏈霉菌屬 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 立體化學 of enoylreduction in modular polyketide synthases.化學 & 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 inStreptomyces sp. DSM4137.化學 & 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 inStreptomyces 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.化學 & Biology 13:945-955.
●Yuhui Sun, Xiufen Zhou, Hui Dong, Guoquan Tu, Min Wang, Bofei Wang and Zixin Deng* (2003) A complete gene cluster fromStreptomyces nanchangensisNS3226 encoding biosynthesis of the polyether 羰基氰化物間氯苯腙 nanchangmycin.化學 & 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 fromStreptomyces nanchangensisNS3226.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 溫度sensitive for replication inStreptomyces 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 ofStreptomyces hygroscopicus 10-22 deduced by analysis of overlapping large chromosomal deletions.Journal of 細菌學 184:1958-1965.
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