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Salinipyrone and Pacificanone Are Biosynthetic By-products of the Rosamicin Polyketide Synthase.

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.

SUBMITTER: Awakawa T

PROVIDER: S-EPMC4545249 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Salinipyrone and Pacificanone Are Biosynthetic By-products of the Rosamicin Polyketide Synthase.

Awakawa Takayoshi T Crüsemann Max M Munguia Jason J Ziemert Nadine N Nizet Victor V Fenical William W Moore Bradley S BS

Chembiochem : a European journal of chemical biology 20150515 10

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 ...[more]

PMID: 25930739

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