Resistance gene-guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases.

ABSTRACT: With the significant increase in the availability of microbial genome sequences in recent years, resistance gene-guided genome mining has emerged as a powerful approach for identifying natural products with specific bioactivities. Here, we present the use of this approach to reveal the roseopurpurins as potent inhibitors of cyclin-dependent kinases (CDKs), a class of cell cycle regulators implicated in multiple cancers. We identified a biosynthetic gene cluster (BGC) with a putative resistance gene with homology to human CDK2. Using targeted gene disruption and transcription factor overexpression in Aspergillus uvarum, and heterologous expression of the BGC in Aspergillus nidulans, we demonstrated that roseopurpurin C (1) is produced by this cluster and characterized i

SUBMITTER: Dunbar KL 

PROVIDER: S-EPMC10691236 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature