Fig. 1.
Structure and biosynthesis of a novel bioactive decadepsipeptide. (A) Structure, molecular mass and growth inhibition potency of compound 1, a new decadepsipeptide produced by Chaetosphaeria tulasneorum. Dose–response curves for HCT116 and yeast cells are shown in Fig. 4B and supplementary material Fig. S1. In addition, the domain organization and proposed assembly line of the matching NPRS is shown. A, adenylation; C, condensation; CT, terminal condensation; PCP, peptidyl carrier protein; M, methylation. Backbone methylations are labelled A–D in the structures. The peptide intermediates are attached as thioesters to the PCP domains. (B) Modules and specificity signatures of the A-domain binding pockets in the matching NPRS. (C) Genomic context of the NRPS for the decadepsipeptide (Orf3): Orf2, pipecolate oxidase; Orf4, 2-hydroxyacid dehydrogenase; Orf5, 2-isopropylmalate synthase; Orf1 and Orf6, other NRPSs. DNA and protein sequences are provided in supplementary material Table S1.