The expanding CRISPR toolbox for natural product discovery and engineering in filamentous fungi

Abstract

Covering: up to May 2022 Fungal genetics has transformed natural product research by enabling the elucidation of cryptic metabolites and biosynthetic steps. The enhanced capability to add, subtract, modulate, and rewrite genes via CRISPR/Cas technologies has opened up avenues for the manipulation of biosynthetic gene clusters across diverse filamentous fungi. This review discusses the innovative and diverse strategies for fungal natural product discovery and engineering made possible by CRISPR/Cas-based tools. We also provide a guide into multiple angles of CRISPR/Cas experiment design, and discuss current gaps in genetic tool development for filamentous fungi and the promising opportunities for natural product research.