Targeted genome mining for microbial antitumor agents acting through DNA intercalation

Autor: Zhijie Zhao, Guiyun Zhao, Yi Chai, Wei Li, Kaihui Song, Wenbin Zhao, Hairong Li, Miaolian Wu, Zhan Zhou, Yi-Ling Du
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Synthetic and Systems Biotechnology, Vol 8, Iss 3, Pp 520-526 (2023)
Druh dokumentu: article
ISSN: 2405-805X
DOI: 10.1016/j.synbio.2023.07.003
Popis: Microbial natural products have been one of the most important sources for drug development. In the current postgenomic era, sequence-driven approaches for natural product discovery are becoming increasingly popular. Here, we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities. Our method employs uvrA-like genes as genetic markers, which have been identified in the biosynthetic gene clusters (BGCs) of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers. Through systematic genomic analysis of gifted actinobacteria genera, identification of uvrA-like gene-containing BGCs, and targeted isolation of products from a BGC prioritized for metabolic analysis, we identified a new tetracycline-type DNA intercalator timmycins. Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation.
Databáze: Directory of Open Access Journals