In vivo investigation of the role of SfmO2 in saframycin A biosynthesis by structural characterization of the analogue saframycin O

作     者：PENG Chao TANG Yu-Min LI Lei DING Wei DENG Wei PU Jin-Yue LIU Wen TANG Gong-Li 

作者机构：State Key Laboratory of Bio-organic and Natural Products ChemistryShanghai Institute of Organic Chemistry Chinese Academy of SciencesShanghai 200032China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2012年第55卷第1期

页      面：90-97页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：supported in part by grants from the National Natural Science Foundation of China(20832009,and 20921091) the Chinese Academy of Sciences and Open Funding Project of the State Key Laboratory of Bioreactor Engineering 

主　　题：saframycin A biosynthesis SfmO2 oxygenase saframycin O 

摘      要：Saframycin A(SFM-A),a tetrahydroisoquinoline antibiotic isolated from Streptomyces lavendulae,shows potent anti-proliferation activities against a variety of tumor cell lines,and shares the core structure with ecteinascidin 743(ET-743),the anticancer drug for soft-tissue *** of the SFM-A biosynthetic gene cluster revealed three nonribosomal peptide synthetase genes and a series of genes encoding *** investigate the function of sfmO2 gene,encoding a FAD-dependent monooxygenase/hydroxylase,we constructed the gene replacement mutant(△sfmO2) strain *** TL2007 and the corresponding gene complementation mutant strain *** TL2008.A novel compound,SFM-O,was isolated from the △sfmO2 replacement mutant strain and its structure was characterized by comparison to the HRMS and NMR spectra of *** findings indicated that SfmO2 is responsible for the oxidation of ring A in the biosynthetic pathway of SFM-A,and the new compound SFM-O could be considered as an advanced intermediate in the semisynthesis of ET-743.