文献类型：期刊文献

英文题名：Identification and Proposed Relative and Absolute Configurations of Niphimycins C-E from the Marine-Derived Streptomyces sp IMB7-145 by Genomic Analysis

作者：Hu, Yuanyuan[1,2];Wang, Mian[1,2];Wu, Chunyan[1,2,3];Tan, Yi[1,2];Li, Jiao[1,2];Hao, Xiaomeng[1,2];Duan, Yanbo[1,2];Guan, Yan[1,2];Shang, Xiaoya[3];Wang, Yiguang[1,2];Xiao, Chunling[1,2];Gan, Maoluo[1,2]

第一作者：Hu, Yuanyuan

通讯作者：Gan, ML[1];Gan, ML[2]

机构：[1]Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China;[2]Peking Union Med Coll, Beijing 100050, Peoples R China;[3]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China

第一机构：Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China

通讯机构：[1]corresponding author), Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China;[2]corresponding author), Peking Union Med Coll, Beijing 100050, Peoples R China.

年份：2018

卷号：81

期号：1

起止页码：178-187

外文期刊名：JOURNAL OF NATURAL PRODUCTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000423778900024)】；

基金：This work was financially supported by the National Natural Science Foundation of China (Grant No. 81273414), CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-2-002), the Chinese National S&T Special Project on Major New Drug Innovation (Grant Nos. 2017ZX09101003-007-002 and 2015ZX09304006-016), and PUMC Youth Fund (3332016062). We thank Prof. Y. Sun of Wuhan University for helpful discussions.

语种：英文

摘要：Analysis of the whole genome sequence of Streptomyces sp. IMB7-145 revealed the presence of seven type I polyketide synthase biosynthetic gene clusters, one of which was highly homologous to the biosynthetic gene cluster of azalomycin F. Detailed bioinformatic analysis of the modular organization of the PKS gene suggested that this gene is responsible for niphimycin biosynthesis. Guided by genomic analysis, a large-scale cultivation ultimately led to the discovery and characterization of four new niphimycin congeners, namely, niphimycins C-E (1-3) and 17-O-methyl-niphimycin (4). The configurations of most stereocenters of niphimycins have not been determined to date. In the present study, the relative configurations were elucidated by spectroscopic analysis, including J-based analysis and the CNMR database method. Further, the full absolute configurations of niphimycins were completely proposed for the first time based on biosynthetic gene cluster analysis of the ketoreductase and enoylreductase domains for hydroxy- and methyl-bearing stereocenters. Compounds 1, 3, 4, and niphimycin I alpha (5) showed antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (MIC: 8-64 mu g/mL), as well as cytotoxicity against the human HeLa cancer cell line (IC50: 3.0-9.0 mu M). In addition, compounds 1 and 5 displayed significant activity against several Mycobacterium tuberculosis clinical isolates (MIC: 4-32 mu g/mL).