Activating natural product synthesis using CRISPR interference and activation systems in Streptomyces.

ABSTRACT: The rise of antibiotic-resistant bacteria represents a major threat to global health, creating an urgent need to discover new antibiotics. Natural products derived from the genus Streptomyces represent a rich and diverse repertoire of chemical molecules from which new antibiotics are likely to be found. However, a major challenge is that the biosynthetic gene clusters (BGCs) responsible for natural product synthesis are often poorly expressed under laboratory culturing conditions, thus preventing the isolation and screening of novel chemicals. To address this, we describe a novel approach to activate silent BGCs through rewiring endogenous regulation using synthetic gene regulators based upon CRISPR-Cas. First, we refine CRISPR interference (CRISPRi) and create CRISPR activation (CRISPRa)

SUBMITTER: Ameruoso A 

PROVIDER: S-EPMC9303295 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature