|Title||Nature's combinatorial biosynthesis produces vatiamides A-F|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Moss N.A, Seiler G., Leao T.F, Castro-Falcon G., Gerwick L, Hughes CC, Gerwick WH|
|Type of Article||Article|
|Keywords||biosynthesis; chemistry; combinatorial biosynthesis; cyanobacteria; docking; gene-cluster; mechanism; non-ribosomal peptides; polyketide synthase; polyketides; reveals|
Hybrid typeI 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.