Nature's Combinatorial Biosynthesis Produces Vatiamides A–F. (28th May 2019)

• Record Type: Journal Article
• Authors: Moss, Nathan A.; Seiler, Grant; Leão, Tiago F.; Castro‐Falcón, Gabriel; Gerwick, Lena; Hughes, Chambers C.; Gerwick, William H.
• Is Part Of: Angewandte Chemie. Volume 131:Number 27(2019)
• Page Start: 9125
• Page End: 9129
• Publication Date: 2019-05-28
• Subjects: Biosynthese -- Cyanobakterien -- Kombinatorische Biosynthese -- Nichtribosomale Peptide -- Polyketide; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201902571
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Hybrid type I PKS/NRPS biosynthetic pathways typically proceed in a collinear manner wherein one molecular building block is enzymatically incorporated in a sequence that corresponds to gene arrangement. In this work, genome mining combined with the use of a fluorogenic azide‐based click probe led to the discovery and characterization of vatiamides A–F, three structurally diverse alkynylated lipopeptides, and their brominated analogues, from the cyanobacterium Moorea producens ASI16Jul14‐2. These derive from a unique combinatorial non‐collinear PKS/NRPS system encoded by a 90 kb gene cluster in which an upstream PKS cassette interacts with three separate cognate NRPS partners. This is facilitated by a series of promiscuous intermodule PKS‐NRPS docking motifs possessing identical amino acid sequences. This interaction confers a new type of combinatorial capacity for creating molecular diversity in microbial systems. Abstract : Kombi‐Dock : Ein einzigartiges Beispiel für die kombinatorische Biosynthese mit einer Polyketidsynthase/nichtribosomalen Peptidsynthese wird beschrieben. Die Vatiamide aus dem Cyanobakterium Moorea producens werden von einem PKS/NRPS‐System produziert, für das ein 90‐kb‐Gencluster kodiert; die kodierten Enzyme interagieren über promiskuitive Andockdomänen mit identischer Sequenz, um drei verschiedene Naturstoffserien zu produzieren.