天然产物独特结构单元的生物合成机制研究基金科学网构建全球华人科学社区,EditSprings,艾德思

 国家自然科学基金项目查询 批准号 20832009 学科分类 生物催化与生物合成 ( B020706 ) 负责人 刘文 职称 研究员 单位名称 中国科学院上海有机化学研究所 资助金额 200万元 项目类别 重点项目 起止年月 2009年01月01日 至 2012年12月31日 主题词 独特结构单元;天然产物;生物合成;结构基因;组合生物合成 附注说明 基于微生物来源天然产物在新药开发方面不可替代的重要性和所具有的独特结构单元与其良好生物活性之间的必然联系,我们拟以部分来源于微生物/结构新颖的活性天然产物为目标,运用微生物学/分子生物学/生物化学/遗传学和化学等多种方式和手段,克隆负责独特结构单元形成或修饰的结构基因,阐明其功能及编码蛋白的酶催化机制,建立生物合成的代谢途径;并运用组合生物合成的原理和方式,探索通过代谢途径的重组获得理化性质得以改善的结构类似物/并采用微生物发酵可以大量积累的新途径. 成果 序号 课题 类型 参与人 0 Characterization of NocL Involved in Thiopeptide Nocathiacin I Biosynthesis A [4Fe-4S] CLUSTER AND THE CATALYSIS OF A RADICAL S-ADENOSYLMETHIONINE ENZYME 期刊 Zhang, Qi, Chen, Dandan, Lin, Jun, Liao, Rijing, Tong, Wei, Xu, Zhinan, Liu, Wen 1 NosA Catalyzing Carboxyl-Terminal Amide Formation in Nosiheptide Maturation via an Enamine Dealkylation on the Serine-Extended Precursor Peptide 期刊 Yu, Yi, Guo, Heng, Zhang, Qi, Duan, Lian, Ding, Ying, Liao, Rijing, Lei, Chun, Shen, Ben, Liu, Wen 2 Toward steadfast growth of antibiotic research in China: From natural products to engineered biosynthesis 期刊 Qianjin Kang, Linquan Bai, Zixin Deng 3 Transcriptome Mining of Active Biosynthetic Pathways and Their Associated Products in Streptomyces flaveolus 期刊 Qu, Xudong, Lei, Chun, Liu, Wen 4 ThioFinder: A Web-Based Tool for the Identification of Thiopeptide Gene Clusters in DNA Sequences 期刊 Jing Li, Xudong Qu, Xinyi He, Lian Duan, Guojun Wu, Dexi Bi, Zixin Deng, Wen Liu, Hong- Yu Ou 5 Engineering of an industrial polyoxin producer for the rational production of hybrid peptidyl nucleoside antibiotics 期刊 Lipeng Zhai, Shuangjun Lin, Dongjing Qu, Xuechuan Hong, Linquan Bai, Wenqing Chen, Zixin Deng 6 Alternative epimerization inC7N-aminocyclitol biosynthesis is catalyzed by ValD, a large protein of thevicinal oxygen chelate superfamily 期刊 Hui Xu, Yirong Zhang, Jongtae Yang, Taifo Mahmud, Linquan Bai, Zixin Deng 7 Functional characterization of the first twoactinomycete 4-amino-4-deoxychorismate lyase genes. 期刊 Yirong Zhang, Linquan Bai, Zixin Deng 8 Genetically engineered production of 1,1′-bis-valienamine and validienamycin in Streptomyces hygroscopicus and their conversion to valienamine 期刊 Hui Xu, Jongtae Yang, Linquan Bai, Zixin Deng, Taifo Mahmud 9 Nosiheptide Biosynthesis Featuring a Unique Indole Side Ring Formation on the Characteristic Thiopeptide Framework 期刊 Yu, Yi, Liu, Wen, Duan, Lian, Zhang, Qi, Liao, Rijing, Ding, Ying, Pan, Haixue, Wendt-Pienkowski, Evelyn, Tang, Gongli, Shen, Ben 10 Biosynthetic Pathway for High Structural Diversity of a Common Dilactone Core in Antimycin Production 期刊 Yan, Yan, Zhang, Lihan, Ito, Takuya, Qu, Xudong, Asakawa, Yoshinori, Awakawa, Takayoshi, Abe, Ikuro, Liu, Wen 11 Analysis of YM-216391 biosynthetic gene cluster and improvement of the cyclopeptide production in a heterologous host 期刊 Jian Xiaohong, Pan Haixue, Ning Tingting, Shi Yuanyuan, Li Yan, Zeng Xiaowei, Xu Jian, Tang, Gongli 12 Thiopeptide Biosynthesis Featuring Ribosomally Synthesized Precursor Peptides and Conserved Posttranslational Modifications 期刊 Liao, Rijing, Liu, Wen, Duan, Lian, Lei, Chun, Pan, Haixue, Ding, Ying, Zhang, Qi, Chen, Daijie, Shen, Ben, Yu, Yi 13 Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B. 期刊 Wei Ding, Wei Deng, Mancheng Tang, Qi Zhang, Gongli Tang, Yurong Bi, Wen Liu 14 Cloning and elucidation of the FR901464 gene cluster revealing a complex acyltransferase-less polyketide synthase using glycerate as starter units 期刊 Zhang Feng, He Haiyan, Tang Mancheng, Tang Yumin, Zhou Qiang, Tang Gongli 15 Self-resistance to antitumor antibiotic: a DNA glycosylase triggers the base excision repair system in yatakemycin biosynthesis. 期刊 Xu Hui, Huang Wei, He Qingli, Zhao Zhixiong, Zhang Feng, Wang Renxiao, Kang Jingwu, Tang, Gongli 16 Biosynthesis of 3,5-AHBA-derived natural products 期刊 Qianjin Kang, Yuemao Shen, Linquan Bai 17 Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation 期刊 Wei Ding, Chun Lei, Qingli He, Qinglin Zhang, Yurong Bi, Wen Liu 18 Structural and Functional Analysis of Validoxylamine A 79-phosphate Synthase ValL Involved in Validamycin A Biosynthesis 期刊 Lina Zheng, Xiang Zhou, Huaidong Zhang, Xiaofeng Ji, Lei Li, Lin Huang, Linquan Bai, Houjin Zhang 19 Radical-mediated enzymatic carbon chain fragmentation-recombination 期刊 Zhang, Qi, Li, Yuxue, Chen, Dandan, Yu, Yi, Duan, Lian, Shen, Ben, Liu, Wen 20 Toward Improvement of Erythromycin A Production in an Industrial Saccharopolyspora erythraea Strain via Facilitation of Genetic Manipulation with an Artificial attB Site for Specific Recombination 期刊 Wu, Jiequn, Zhang, Qinglin, Deng, Wei, Qian, Jiangchao, Zhang, Siliang, Liu, Wen 21 Characterization of SfmD as a heme peroxidase that catalyzes the regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine in saframycin A biosynthesis. 期刊 Tang Mancheng, Fu Chengyu, Tang gongli 22 Insights into Pyrroindomycin Biosynthesis Reveal a Uniform Paradigm for Tetramate/Tetronate Formation 期刊 Qiongqiong Wu, Zhuhua Wu, Xudong Qu, Wen Liu 23 Thiostrepton Maturation Involving a Deesterification-Amidation Way To Process the C-Terminally Methylated Peptide Backbone 期刊 Liao, Rijing, Liu, Wen 24 Identification of phoslactomycin biosynthetic gene clusters from Streptomyces platensis SAM-0654 and characterization of PnR1 and PnR2 as positive transcriptional regulators. 期刊 Chen Yunliang, Zhao Juan, Liu wei, Gao Junfang, Tao Liming, Pan, Haixue, Tang Gongli 25 Caerulomycins and Collismycins Share a Common Paradigm for 2,2 '-Bipyridine Biosynthesis via an Unusual Hybrid Polyketide-Peptide Assembly Logic 期刊 Qu, Xudong, Liu, Wen, Pang, Bo, Zhang, Zhicong, Chen, Ming, Wu, Zhuhua, Zhao, Qunfei, Zhang, Qinglin, Wang, Yinyan, Liu, Yun 26 Cloning and Characterization of the Polyether Salinomycin Biosynthesis Gene Cluster of Streptomyces albus XM211 期刊 Chunyan Jiang, Hougen Wang, Qianjin Kang, Jing Liu, Linquan Bai 27 Characterization of the Polyoxin Biosynthetic Gene Cluster from Streptomyces cacaoi and Engineered Production of Polyoxin H 期刊 Wenqing Chen, Huchen Zhou, Xiufen Zhou, Huarong Tan, Zixin Deng, Tingting Huang, Xinyi He, Qingqing Meng, Delin You, Linquan Bai, Jialiang Li, Mingxuan Wu, Rui Li 28 Moving posttranslational modifications forward to biosynthesize the glycosylated thiopeptide nocathiacin I in Nocardia sp ATCC202099 期刊 Ding, Ying, Yu, Yi, Pan, Haixue, Guo, Heng, Li, Yeming, Liu, Wen 29 In vivo investigation of the role of SfmO2 in saframycin A biosynthesis by structural characterization of the analogue saframycin O 期刊 Peng Chao, Tang Yunmin, Li Lei, Ding Wei, Deng Wei, Pu Jinyue, Liu, Wen, Tang, Gongli 30 Characterization of the Biosynthesis Gene Cluster for the Pyrrole Polyether Antibiotic Calcimycin (A23187) in Streptomyces chartreusis NRRL 3882 期刊 Qiulin Wu, Jingdan Liang, Shuangjun Lin, Xiufen Zhou, Linquan Bai, Zixin Deng, Zhijun Wang 31 Radical-Mediated Enzymatic Methylation: A Tale of Two SAMS 期刊 Zhang, Qi, van der Donk, Wilfred A., Liu, Wen 32 抗肿瘤活性四氢异喹啉抗生素的生物合成研究进展 期刊 唐满成, 唐功利 33 Nucleotidylation of unsaturated carbasugar in validamycin biosynthesis 期刊 Jongtae Yang, Hui Xu, Yirong Zhang, Linquan Bai, Zixin Deng, Taifo Mahmud 34 Quartromicin biosynthesis: two alternative polyketide chains produced by one polyketide synthase assembly line 期刊 He Haiyan, Pan Haixue, Wu Longfei, Zhang Beibei, Chai Hanbo, Liu Wen, Tang Gongli 35 Dual Carbamoylations on the Polyketide and Glycosyl Moiety by Asm21 Result in Extended Ansamitocin Biosynthesis 期刊 Yan Li, Peiji Zhao, Qianjin Kang, Juan Ma, Linquan Bai, Zixin Deng 36 Improvement of FK506 Production in Streptomyces tsukubaensis by Genetic Enhancement of the Supply of Unusual Polyketide Extender Units via Utilization of Two Distinct Site-Specific Recombination Systems 期刊 Chen, Dandan, Zhang, Qi, Zhang, Qinglin, Cen, Peilin, Xu, Zhinan, Liu, Wen 37 Complex Biotransformations Catalyzed by Radical S-Adenosylmethionine Enzymes 期刊 Zhang, Qi, Liu, Wen 38 Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line. 期刊 Peng Chao, Pu Jinyue, Song Liqiang, Jian Xiaohong, Tang Mancheng, Tang Gongli 39 Characterization of yatakemycin gene cluster revealing a radical S-adenosylmethionine dependent methyltransferase and highlighting spirocyclopropane biosynthesis 期刊 Huang Wei, Xu Hui, Li Yan, Zhang Feng, Chen Xinya, He Qingli, Igarashi Yasuhiro, Tang, Gongli 40 Cloning, sequencing and characterization of the biosynthetic gene cluster of sanglifehrin A, a potent cyclophilin inhibitor 期刊 Qu, Xudong, Jiang, Nan, Xu, Fei, Shao, Lei, Tang, Gongli, Wilkinson, Barrie, Liu, Wen 41 Cloning and functional analysis of the naphthomycin biosynthetic gene cluster in Streptomyces sp. CS 期刊 Yingying Wu, Qianjin Kang, Yuemao Shen, Wenjin Su, Linquan Bai 42 Cloning of Separate Meilingmycin Biosynthesis Gene Clusters by Use of Acyltransferase-Ketoreductase Didomain PCR Amplification 期刊 Yunlong He, Yuhui Sun, Tiangang Liu, Xiufen Zhou, Linquan Bai, Zixin Deng 43 Insights into Quinaldic Acid Moiety Formation in Thiostrepton Biosynthesis Facilitating Fluorinated Thiopeptide Generation 期刊 Duan, Lian, Wang, Shoufeng, Liao, Rijing, Liu, Wen 摘要 结题摘要 微生物来源天然产物在新药开发方面有不可替代的重要性.基于其所具有的独特结构单元与良好生物活性之间的必然联系,我们以部分来源于微生物/结构新颖的活性天然产物为目标,运用微生物学/分子生物学/生物化学/遗传学和化学等多种方式和手段,克隆负责独特结构单元形成或修饰的结构基因,阐明其功能及编码蛋白的酶催化机制,建立生物合成的代谢途径.在此基础上,我们运用组合生物合成的原理和方式,探索通过代谢途径的重组获得理化性质得以改善的结构类似物/并采用微生物发酵可以大量积累的新途径.

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