The Isolation of Pyrroloformamide Congeners and Characterization of Their Biosynthetic Gene Cluster

Overview

Journal J Nat Prod

Date 2020 Feb 13

PMID 32049520

Citations 2

Authors

Wenqing Zhou

Haoyu Liang

Xiangjing Qin

Danfeng Cao

Xiangcheng Zhu

Jianhua Ju

Ben Shen

Yanwen Duan

Yong Huang

Affiliations

Soon will be listed here.

Abstract

Dithiolopyrrolones are microbial natural products containing a disulfide or thiosulfonate bridge embedded in a unique bicyclic structure. By interfering with zinc ion homeostasis in living cells, they show strong antibacterial activity against a variety of bacterial pathogens, as well as potent cytotoxicity against human cancer cells. In the current study, two new dithiolopyrrolones, pyrroloformamide C () and pyrroloformamide D (), were isolated from sp. CB02980, together with the known pyrroloformamides and . The biosynthetic gene cluster for pyrroloformamides was identified from sp. CB02980, which shared high sequence similarity with those of dithiolopyrrolones, including holomycin and thiolutin. Gene replacement of , which encodes a nonribosomal peptide synthetase (NRPS), abolished the production of -. Overexpression of , a type II thioesterase gene, increased the production of and . Genome neighborhood network analysis of the characterized and orphan gene clusters of dithiolopyrrolones revealed a unified mechanism for their biosynthesis, involving an iterative-acting NRPS and a set of conserved tailoring enzymes for the bicyclic core formation.

Citing Articles

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