期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 27, 页码 9027-9031出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201902571
关键词
biosynthesis; combinatorial biosynthesis; cyanobacteria; polyketides; non-ribosomal peptides
资金
- NIH [GM118815]
- NIH Training Grant in Marine Biotechnology and Microbiome and Microbial Sciences Initiative Graduate Student Fellowship
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.
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