Abstract:
:New technology for the derivatization of peptide natural products is required for drug development. Despite the recent advances in the genome sequencing technique enabling us to search for the biosynthetic genes for wide variety of natural products, the technical methods to get access to them are limited. A class of RiPPs, a recently emerged natural product family such as thioviridamide, is one of those possessing such unexplored chemical space. In this paper, we report a streamlined method to generate new thioviridamide derivatives and to assess their biological activities. Heterologous expression of 42 constructs in an engineered Streptomyces avermitilis host gave 35 designed thioviridamide derivatives, along with several unprecedented analogues. Moreover, cytotoxicity assay revealed that several derivatives showed more potent activities than those of prethioviridamide. These results indicate that this strategy can become one of the potential ways to produce supreme unnatural products.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Kudo K,Koiwai H,Kagaya N,Nishiyama M,Kuzuyama T,Shin-Ya K,Ikeda Hdoi
10.1021/acschembio.9b00330subject
Has Abstractpub_date
2019-06-21 00:00:00pages
1135-1140issue
6eissn
1554-8929issn
1554-8937journal_volume
14pub_type
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