Genome Mining of Isoindolinone-Containing Peptide Natural Products.

ABSTRACT: Peptide natural products (PNPs) are important sources of bioactive compounds. Recent studies have shown that oligopeptides or pseudopeptides can be synthesized by amide-bond-forming enzymes such as ATP-grasp enzymes and amide-bond synthetases (ABSs). By focusing on ATP-grasp enzymes as part of a conserved biosynthetic enzyme ensemble, genome mining of PNPs was performed on three biosynthetic gene clusters (BGCs) from diverse fungi, including Coccidioides immitis RS, the causative agent of valley fever. We demonstrate that the conserved enzymes synthesize a common dipeptide fragment, l-leucine-l-O-isoindolinone-homoserine (l-Leu-l-Isd), which is modified and diversified into three PNPs (1-3) by associated enzymes in the three pathways. Pathway reconstitution and

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12145162 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature