Strategies for Natural Product Discovery by Unlocking Cryptic Biosynthetic Gene Clusters in Fungi

Abstract

Recent advancements in genome sequencing and bioinformatic analysis of fungal genomes have revealed that fungi possess cryptic or silent biosynthetic gene clusters (BGCs). This discovery suggests that our understanding of the universe of fungal secondary metabolomes is limited. In this review, we summarize recent strategies for activating cryptic BGCs in fungi, identify fungal secondary metabolites, and highlight their biological activities. We also briefly discuss the isolation and purification methods for these compounds. Our focus is on genetics-dependent and genetics-independent approaches for activating cryptic BGCs in fungi. Using the strategies discussed here, cryptic fungal natural products hold significant potential as a source for the discovery of new drug candidates.