Piperazate-Guided Isolation of Caveamides A and B, Cyclohexenylalanine-Containing Nonribosomal Peptides from a Cave Actinomycete.

Hybrid genome-mining/ 15 N-NMR was used to target compounds containing piperazate (Piz) residues, leading to the discovery of caveamides A ( 1 ) and B ( 2 ) from Streptomyces sp. strain BE230, isolated from New Rankin Cave (Missouri). Caveamides are highly dynamic molecules containing an unprecedented β-ketoamide polyketide fragment, two Piz residues, and a new N -methyl-cyclohexenylalanine residue. Caveamide B ( 2 ) exhibited nanomolar cytotoxicity against several cancer cell lines and nanomolar antimicrobial activity against MRSA and E. coli .