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A highly unusual polyketide synthase directs dawenol polyene biosynthesis in Stigmatella aurantiaca

Paper ID Volume ID Publish Year Pages File Format Full-Text
22998 43409 2014 10 PDF Available
Title
A highly unusual polyketide synthase directs dawenol polyene biosynthesis in Stigmatella aurantiaca
Abstract

•Correlation of dawenol production to a highly unusual polyketide pathway.•Similarity to polyunsaturated fatty acid/secondary lipid biosynthetic pathways.•Iterative assembly, incorporation of methylmalonate and unusual chain termination.•In all ACPs the active site serine seems to be functionally replaced by threonine.•Heterologous expression of the dawenol pathway in Myxococcus xanthus.

Enormous progress in the field of polyketide biosynthesis has led to the establishment of rules for general text book biosynthetic logic and consequently to the assumption that biosynthetic genes can be easily correlated with the corresponding natural products. However, non-textbook examples of polyketide assembly continue to be discovered suggesting the gene to product and product to gene predictions need improvement, especially as they are increasingly used in the post-genomic era. Here, we analyzed the genomic blueprint of a myxobacterial multi-producer of secondary metabolites, Stigmatella aurantiaca DW4/3-1, for its biosynthetic potential by genome-mining. In addition to the five polyketide synthase and/or nonribosomal peptide synthetase gene clusters of known function we identified a further 13 genomic regions exemplifying the enormous genetic potential for the production of additional chemical diversity by this strain. We show by gene inactivation and heterologous expression of the newly identified biosynthetic pathway for dawenol that the biosynthesis of this known polyene does not follow text book biosynthetic logic. Intriguingly, a genomic locus encoding an unusual polyketide synthase exhibiting similarity to gene loci involved in the formation of polyunsaturated fatty acids and secondary lipids was identified.

Keywords
Dawenol; Genome-mining; PUFA-like polyketide synthase; Iterative polyketide synthase; Secondary lipid synthase
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A highly unusual polyketide synthase directs dawenol polyene biosynthesis in Stigmatella aurantiaca
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 191, 10 December 2014, Pages 54–63
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us