以具有重要基础和应用价值的微生物天然产物为研究对象,从分子遗传学、生物化学及合成生物学的角度探索其生物合成机理,并回答其生物合成中蕴藏的关键科学问题,为新药创制提供精确的“分子装配线路图”。同时,通过代谢途径的理性设计和定向优化,有的放矢地改造天然产物生物合成途径,实现微生物药物的高产和创新。
Guo Sun, Chaoqun Hu, Qing Mei, Minghe Luo, Xu Chen, Zhengyuan Li, Yuanzhen Liu, Zixin Deng, Zhengyu Zhang* and Yuhui Sun*, Uncovering the cytochrome P450-catalyzed methylenedioxy bridge formation in streptovaricins biosynthesis. Nature Communications 2020, 11: 4501.
Guifa Zhai#, Wenyan Wang#, Wei Xu, Guo Sun, Chaoqun Hu, Xiangming Wu, Zisong Cong, Liang Deng, Yanrong Shi, Peter F. Leadlay, Heng Song, Kui Hong, Zixin Deng and Yuhui Sun*, Cross-module enoylreduction in the azalomycin F polyketide synthase. Angewandte Chemie International Edition 2020, 59: 2-7.
Minghe Luo, Lingjie Tang, Yulu Dong, Hongbo Huang, Zixin Deng and Yuhui Sun*, Antibacterial natural products lobophorin L and M from the marine-derived Streptomyces sp. 4506. Natural Product Research (Online ahead of print).
Yuanzhen Liu*, Xu Chen, Zhengyuan Li, Lixia Huang and Yuhui Sun*, Ansavaricin J, a new heterocyclic ring-fused streptovaricin from gene stvP5-deleted mutant of Streptomyces spectabilis CCTCC M2017417. Chemistry & Biodiversity 2020, 17: e1900713.
Yao Liu#, Yuanzhen Liu#, Zixiu Du#, Lidan Zhang, Juan Chen, Zhen Shen, Qian Liu, Juanxiu Qin, Huiying Lv, Hua Wang, Lei He, Junlan Liu, Qian Huang, Yuhui Sun*, Michael Otto* and Min Li*, Skin microbiota analysis-inspired development of novel anti-infectives. Microbiome 2020, 8: 85.
Sicong Li#, Qian Liu#, Zhiyu Zhong, Zixin Deng and Yuhui Sun*, Exploration of hygromycin B biosynthesis utilizing CRISPR-Cas9-associated base editing. ACS Chemical Biology 2020, 15: 1417-1423.
Rory Little, Fernanda C. R. Paiva, Robert Jenkins, Hui Hong, Yuhui Sun, Yuliya Demydchuk, Markiyan Samborskyy, Manuela Tosin, Finian J. Leeper, Marcio V. B. Dias and Peter F. Leadlay*, Unexpected enzyme-catalysed [4+2] cycloaddition and rearrangement in polyether antibiotic biosynthesis. Nature Catalysis 2019, 2: 1045-1054.
Weixin Tao*, Li Chen, Chunhua Zhao, Jing Wu, Dazhong Yan, Zixin Deng and Yuhui Sun*, In vitro packaging mediated one-step targeted cloning of natural product pathway. ACS Synthetic Biology 2019, 8: 1991-1997.
Zhiyu Zhong#, Junhong Guo#, Liang Deng, Li Chen, Jian Wang, Sicong Li, Wei Xu, Zixin Deng and Yuhui Sun*, Base editing in Streptomyces with Cas9-deaminase fusions. bioRxiv 2019 (doi: https://doi.org/10.1101/630137).
Jingjing Zhou, Chengbin Qiu, Ni Pi, Sicong Li, Xiyao Cheng, Lei Zhang, Yao Chen, Yongqi Huang*, Yuhui Sun* and Zhengding Su*, A protein biosynthesis machinery strategy for identifying P53PTC-rescuing compounds as synergic anti-tumor drugs. ChemistrySelect 2018, 3: 11048-11053.
Weixin Tao, Anna Yang, Zixin Deng and Yuhui Sun*, CRISPR/Cas9-based editing of streptomyces for discovery, characterization, and production of natural products. Frontiers in Microbiology 2018, 9: 1660.
Sicong Li#, Jun Zhang#, Yuanzhen Liu, Guo Sun, Zixin Deng and Yuhui Sun*, Direct genetic and enzymatic evidence for oxidative cyclization in hygromycin B biosynthesis. ACS Chemical Biology 2018, 13: 2203-2210.
Yuan Li#, Wan Zhang#, Hui Zhang, Wenya Tian, Lian Wu, Shuwen Wang, Mengmeng Zheng, Jinru Zhang, Chenghai Sun, Zixin Deng, Yuhui Sun, Xudong Qu* and Jiahai Zhou*, Structural basis of a broadly selective acyltransferase from the polyketide synthase of splenocin. Angewandte Chemie International Edition 2018, 57: 5823-5827.
Sicong Li#, Junhong Guo#, Anna Reva, Fanglu Huang, Binbin Xiong, Yuanzhen Liu, Zixin Deng, Peter F. Leadlay* and Yuhui Sun*, Methyltransferases of gentamicin biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 2018, 115:1340-1345.
Yuanzhen Liu, Xu Chen, Zhengyuan Li, Wei Xu, Weixin Tao, Jie Wu, Jian Yang, Zixin Deng and Yuhui Sun*, Functional analysis of cytochrome P450s involved in streptovaricin biosynthesis and generation of anti-MRSA analogues. ACS Chemical Biology 2017, 12: 2589-2597.
Priscila dos Santos Bury, Fanglu Huang, Sicong Li, Yuhui Sun, Peter F. Leadlay and Marcio Vinicius Bertacine Dias*, Structural basis of the selectivity of GenN, an aminoglycoside N-methyltransferase involved in gentamicin biosynthesis. ACS Chemical Biology 2017, 12: 2779-2787.
Wei Xu#, Guifa Zhai#, Yuanzhen Liu, Yuan Li, Yanrong Shi, Kui Hong, Hui Hong, Peter F. Leadlay, Zixin Deng and Yuhui Sun*, An iterative module in the azalomycin F polyketide synthase contains a switchable enoylreductase domain. Angewandte Chemie International Edition 2017, 56: 5503-5506.
Marie E. Yurkovich, Robert Jenkins, Yuhui Sun, Manuela Tosin* and Peter F. Leadlay*, The polyketide backbone of thiolactomycin is assembled by an unusual iterative polyketide synthase. Chemical Communications 2017, 53: 2182-2185.
Judith Havemann, Marie E. Yurkovich, Robert Jenkins, Sophia Harringer, Weixin Tao, Shishi Wen, Yuhui Sun, Peter F. Leadlay and Manuela Tosin*, Chemical probing of thiotetronate bio-assembly. Chemical Communications 2017, 53: 1912-1915.
Hui Hong, Yuhui Sun, Yongjun Zhou, Emily Stephens, Markiyan Samborskyy and Peter F. Leadlay*, Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase. Beilstein Journal of Organic Chemistry 2016, 12: 2164-2172.
Jianzhao Qi, Dan Wan, Hongmin Ma, Yuanzhen Liu, Rong Gong, Xudong Qu, Yuhui Sun, Zixin Deng and Wenqing Chen*, Deciphering carbamoylpolyoxamic acid biosynthesis reveals unusual acetylation cycle associated with tandem reduction and sequential hydroxylation. Cell Chemical Biology 2016, 23: 935-944.
Yujie Geng, Zixin Deng and Yuhui Sun*, An insight into the protospacer adjacent motif of Streptococcus pyogenes Cas9 with artificially stimulated RNA-guided-Cas9 DNA cleavage flexibility. RSC Advances 2016, 6: 33514-33522.
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*, A genomics-led approach to deciphering the mechanism of thiotetronate antibiotic biosynthesis. Chemical Science 2016, 7: 376-385.
Yunkun Liu#, Weixin Tao#, Shishi Wen, Zhengyuan Li, Anna Yang, Zixin Deng and Yuhui Sun*, In vitro CRISPR/Cas9 system for efficient targeted DNA editing. mBio 2015, 6:e 01714-15.
Hu Zeng, Shishi Wen, Wei Xu, Zhaoren He, Guifa Zhai, Yunkun Liu, Zixin Deng and Yuhui Sun*, 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 2015, 99: 10575-10585.
Chuan Huang#, Fanglu Huang#, Eileen Moison, Junhong Guo, Xinyun Jian, Xiaobo Duan, Zixin Deng, Peter F. Leadlay* and Yuhui Sun*, Delineating the biosynthesis of gentamicin X2, the common precursor of the gentamicin C antibiotic complex. Chemistry & Biology 2015, 22: 251-261.
Junhong Guo#, Fanglu Huang#, Chuan Huang, Xiaobo Duan, Xinyun Jian, Finian Leeper, Zixin Deng, Peter F. Leadlay* and Yuhui Sun*, Specificity and promiscuity at the branch point in gentamicin biosynthesis. Chemistry & Biology 2014, 21:608-618.
Yuhui Sun*, A carbonate architect emerges. Nature Chemical Biology 2014, 10:486-487. (Invited Comments)
Yanling Ma, Wei Xu, Jun Zhang, Sihong Zhang, Kui Hong, Zixin Deng and Yuhui Sun*, Nitrilase superfamily aryl acylamidase from the halotolerant mangrove Streptomyces sp. 211726. Applied Microbiology and Biotechnology 2014, 98: 8583-8590.
Weixin Tao#, Manghong Zhu#, Zixin Deng and Yuhui Sun*, Biosynthesis of tetronate antibiotics: A growing family of natural products with broad biological activities. Science China Chemistry 2013, 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*, Unusual acetylation-elimination in the formation of tetronate antibiotics. Angewandte Chemie International Edition 2013, 52: 5785-5788.
Marie E. Yurkovich, Petros A. Tyrakis, Hui Hong, Yuhui Sun, Markiyan Samborskyy, Kohei Kamiya and Peter F. Leadlay*, A late-stage intermediate in salinomycin biosynthesis is revealed by specific mutation in the biosynthetic gene cluster. ChemBioChem 2012, 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*, An additional dehydratase-like activity is required for lankacidin antibiotic biosynthesis. ChemBioChem 2011, 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
Yunlong He, Yuhui Sun, Tiangang Liu, Xiufen Zhou, Linquan Bai* and Zixin Deng, Cloning of separate meilingmycin biosynthesis gene clusters by use of acyltransferase-ketoreductase didomain PCR amplification. Applied and Environmental Microbiology 2010, 76: 3283-3292.
Yuhui Sun*, Frank Hahn, Yuliya Demydchuk, James Chettle, Manuela Tosin, Hiroyuki Osada and Peter F. Leadlay*, In vitro reconstruction of tetronate RK-682 biosynthesis. Nature Chemical Biology 2010, 6: 99-101.注:本论文被英国Faculty of 1000收录(http://f1000.com/)并获专家正面点评。
Yuhui Sun, Xinyi He, Jingdan Liang, Xiufen Zhou and Zixin Deng*, Analysis of functions in plasmid pHZ1358 influencing its genetic and structural stability in Streptomyces lividans 1326. Applied Microbiology and Biotechnology 2009, 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*, Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases. Chemistry & Biology 2008, 15: 1231-1240.
Yuliya Demydchuk#, Yuhui Sun#, Hui Hong, James Staunton, Jonathan B. Spencer and Peter F. Leadlay*, Analysis of the tetronomycin gene cluster: insights into the biosynthesis of a polyether tetronate antibiotic. ChemBioChem 2008, 9: 1136-1145.
Yuhui Sun, Hui Hong, Fraser Gillies, Jonathan B. Spencer and Peter F. Leadlay*, Glyceryl-S-acyl carrier protein as an intermediate in the biosynthesis of tetronate antibiotics. ChemBioChem 2008, 9: 150-156.
Barbara M. Harvey, Tatiana Mironenko, Yuhui Sun, Hui Hong, Zixin Deng, Peter F. Leadlay, Kira J. Weissman and Stephen F. Haydock*, Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137. Chemistry & Biology 2007, 14: 703-714.
Yuhui Sun, Hui Hong, Markiyan Samborskyy, Tatiana Mironenko, Peter F. Leadlay and Stephen F. Haydock*, Organization of the biosynthetic gene cluster in Streptomyces sp. DSM 4137 for the novel neuroprotectant polyketide meridamycin. Microbiology 2006, 152: 3507-3515.
Tiangang Liu, Delin You, Chiara Valenzano, Yuhui Sun, Jialiang Li, Qing Yu, Xiufen Zhou, David E. Cane and Zixin Deng*, Identification of NanE as the thioesterase for polyether chain release in nanchangmycin biosynthesis. Chemistry & Biology 2006, 13:945-955.
Yuhui Sun, Xiufen Zhou, Hui Dong, Guoquan Tu, Min Wang, Bofei Wang and Zixin Deng*, A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin. Chemistry & Biology 2003, 10: 431-441.
Yuhui Sun, Xiufen Zhou, Guoquan Tu and Zixin Deng*, Identification of a gene cluster encoding meilingmycin biosynthesis among multiple polyketide synthase contigs isolated from Streptomyces nanchangensis NS3226. Archives of Microbiology 2003, 180: 101-107.
Yuhui Sun, Xiufen Zhou, Jun Liu, Kai Bao, Guiming Zhang, Guoquan Tu, Tobias Kieser and Zixin Deng*, ‘Streptomyces nanchangensis’, a producer of the insecticidal polyether antibiotic nanchangmycin and the antiparasitic macrolide meilingmycin, contains multiple polyketide gene clusters. Microbiology 2002, 148: 361-371.
Xiuhua Pang, Xiufen Zhou, Yuhui Sun and Zixin Deng*, Physical map of the linear chromosome of Streptomyces hygroscopicus 10-22 deduced by analysis of overlapping large chromosomal deletions. Journal of Bacteriology 2002, 184: 1958-1965.
Xiuhua Pang, Yuhui Sun, Liu Jun, Xiufen Zhou and Zixin Deng*, A linear plasmid temperature-sensitive for replication in Streptomyces hygroscopicus 10-22. FEMS Microbiology Letters 2002, 208: 25-28.
剑桥大学生物化学系Herchel Smith讲席教授、英国皇家学会院士(FRS)、英国皇家化学会院士(FRSC)Peter F. Leadlay (http://www.bio.cam.ac.uk/~pflgroup/)