Multiplex Base-Editing Enables Combinatorial Epigenetic Regulation for Genome Mining of Fungal Natural Products.

ABSTRACT: Genome mining of cryptic natural products (NPs) remains challenging, especially in filamentous fungi, owing to their complex genetic regulation. Increasing evidence indicates that several epigenetic modifications often act cooperatively to control fungal gene transcription, yet the ability to predictably manipulate multiple genes simultaneously is still largely limited. Here, we developed a multiplex base-editing (MBE) platform that significantly improves the capability and throughput of fungal genome manipulation, leading to the simultaneous inactivation of up to eight genes using a single transformation. We then employed MBE to inactivate three negative epigenetic regulators combinatorially in Aspergillus nidulans, enabling the activation of eight cryptic gene clusters compared to

SUBMITTER: Zhao F 

PROVIDER: S-EPMC10162584 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature