Allopeptimicins: unique antibacterial metabolites generated by hybrid PKS-NRPS, with original self-defense mechanism in Actinoallomurus. Issue 26 (6th June 2022)

• Record Type: Journal Article
• Authors: Iorio, Marianna; Gentile, Andrea; Brunati, Cristina; Tocchetti, Arianna; Landini, Paolo; Maffioli, Sonia Ilaria; Donadio, Stefano; Sosio, Margherita
• Is Part Of: RSC advances. Volume 12:Issue 26(2022)
• Page Start: 16640
• Page End: 16655
• Publication Date: 2022-06-06
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2ra02094g
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Untargeted metabolomic analysis of Actinoallomurus spp. unveiled an unprecedented acylated cyclodepsipeptide with unusual features and potent antibacterial activity. Abstract : In the search for structurally novel metabolites with antibacterial activity, innovative approaches must be implemented to increase the probability of discovering novel chemistry from microbial sources. Here we report on the application of metabolomic tools to the genus Actinoallomurus, a poorly explored member of the Actinobacteria. From examining extracts derived from 88 isolates belonging to this genus, we identified a family of cyclodepsipeptides acylated with a C20 polyketide chain, which we named allopeptimicins. These molecules possess unusual structural features, including several double bonds in the amino-polyketide chain and four non-proteinogenic amino acids in the octapeptide. Remarkably, allopeptimicins are produced as a complex of active and inactive congeners, the latter carrying a sulfate group on the polyketide amine. This modification is also a mechanism of self-protection in the producer strain. The structural uniqueness of allopeptimicins is reflected in a biosynthetic gene cluster showing a mosaic structure, with dedicated gene cassettes devoted to formation of specialized precursors and modular assembly lines related to those from different pathways.