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Discovery of New Thioviridamide‐Like Compounds with Antitumor Activities
Author(s) -
Li Yuqing,
Liu Jingyu,
Tang Haoyu,
Qiu Yanping,
Chen Dandan,
Liu Wen
Publication year - 2019
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201900235
Subject(s) - chemistry , biosynthesis , gene , natural product , gene cluster , genome , computational biology , biochemistry , secondary metabolite , enzyme , combinatorial chemistry , stereochemistry , biology
Summary of main observation and conclusion Thioviridamide is a structurally unique compound with potent antitumor activity. The biosynthesis of thioviridamide follows a typical pathway as ribosomally synthesized and post‐translationally modified peptides, making the genome mining‐based discovery of thioviridamide‐like compounds rational. Taking advantage of the linkage between the precursor peptide and the metabolite skeleton, we identified a new biosynthetic gene cluster in Streptomyce s sp. NRRL S‐87 that could encode thioviridamide analogues. Overexpression of the whole gene cluster led to the isolation and structure elucidation of TVA‐YJ‐4 and TVA‐YJ‐5, two novel thioviridamide‐like compounds featuring N ‐terminal capping groups. Chemical screening of the fermentation extracts also detected TVA‐YJ‐6, another new thioviridamide‐like compound with representative methionine sulfoxide. Detailed analysis further revealed that these structural modifications were introduced during the compound extraction process instead of through genuine enzymatic reactions. TVA‐YJ‐4 and TVA‐YJ‐5 display slightly reduced cytotoxic activities against a panel of tumor cell lines in comparison with their parental natural product, TVA‐YJ‐2. Our work will expand the membership of this rare class of compounds and promote related biosynthetic studies.