Comprehensive Derivatization of Thioviridamides by Heterologous Expression.

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 Biol

journal_title

ACS chemical biology

authors

Kudo K,Koiwai H,Kagaya N,Nishiyama M,Kuzuyama T,Shin-Ya K,Ikeda H

doi

10.1021/acschembio.9b00330

subject

Has Abstract

pub_date

2019-06-21 00:00:00

pages

1135-1140

issue

6

eissn

1554-8929

issn

1554-8937

journal_volume

14

pub_type

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