Journal
CHINESE JOURNAL OF CHEMISTRY
Volume 37, Issue 10, Pages 1015-1020Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cjoc.201900235
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Funding
- NSFC [21750004, 31430005, 21520102004, 21621002]
- CAS [SQYZDJ-SSW-SLH1037, XDB20020200]
- STCM [17JC1405100, 15JC1400400]
- Drug Innovation Major Project [2018ZX09711001-006-010]
- K. C. Wong Education Foundation
- Youth Innovation Promotion Association CAS of China [2017303]
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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 Streptomyces 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.
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