Salinipyrone and pacificanone are biosynthetic by-products of the rosamicin polyketide synthase

TitleSalinipyrone and pacificanone are biosynthetic by-products of the rosamicin polyketide synthase
Publication TypeJournal Article
Year of Publication2015
AuthorsAwakawa T., Crusemann M., Munguia J., Ziemert N., Nizet V., Fenical W, Moore BS
JournalChembiochem
Volume16
Pagination1443-1447
Date Published2015/07
Type of ArticleArticle
ISBN Number1439-4227
Accession NumberWOS:000357326200009
Keywordsabsolute-configuration; actinomycete genus salinispora; antibiotics; biosynthesis; cytochrome-p450; diversity; macrolactone; macrolide; macrolide antibiotics; model; mycg; mycinamicins; polyketide synthases; Salinispora; x-ray crystallography
Abstract

Salinipyrones and pacificanones are structurally related polyketides from Salinispora pacifica CNS-237 that are proposed to arise from the same modular polyketide synthase (PKS) assembly line. Genome sequencing revealed a large macrolide PKS gene cluster that codes for the biosynthesis of rosamicin A and a series of new macrolide antibiotics. Mutagenesis experiments unexpectedly correlated salinipyrone and pacificanone biosynthesis to the rosamicin octamodule Spr PKS. Remarkably, this bifurcated polyketide pathway illuminates a series of enzymatic domain- and module-skipping reactions that give rise to natural polyketide product diversity. Our findings enlarge the growing knowledge of polyketide biochemistry and illuminate potential challenges in PKS bioengineering.

DOI10.1002/cbic.201500177
Short TitleChemBioChem
Student Publication: 
No
Research Topics: 
sharknado