title: The methoxymalonyl-acyl carrier protein biosynthesis locus and the nearby gene with the beta-ketoacyl synthase domain are involved in the biosynthesis of galbonolides in Streptomyces galbus, but these loci are separate from the modular polyketide synthase gene cluster.
abstract: Galbonolides A and B are antifungal compounds, which are produced by Streptomyces galbus. A multimodular polyketide synthase (PKS) was predicted to catalyze their biosynthesis, and a methoxymalonyl-acyl carrier protein (methoxymalonyl-ACP) was expected to be involved in the biosynthesis of galbonolide A. Cloning of a methoxymalonyl-ACP biosynthesis locus (galGHIJK) and the flanking regions has revealed that the locus is colocalized with beta-ketoacyl synthase (KAS)-related genes (orf3, 4, and 5), but separated from any multimodular PKS gene cluster in S. galbus. A galI-disruption mutant (SK-galI-5) is unable to produce galbonolide A, but can synthesize galbonolide B, indicating that galGHIJK is involved in the biosynthesis of galbonolide A. A disruption mutant of orf4 is severely impaired in the production of both galbonolides A and B. These results indicate that galGHIJK and the KAS genes are involved in the biosynthesis of galbonolides, although they are not colocalized with a multimodular PKS gene cluster. We further propose that a single galbonolide PKS generates two discrete structures, galbonolides A and B, by alternatively incorporating methoxymalonate and methylmalonate, respectively.
authors.affiliation: Department of Biological Science, Division of Bioscience and Bioinformatics, Myongji University, San 38-2 Nam-dong, Yongin-si, Gyunggi-do, Korea.
authors.forename: Suman
authors.initials: S
authors.lastname: Karki
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Kwon
authors.forename: Hye-Gyeong
authors.initials: HG
authors.lastname: Yoo
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
authors.forename: Si-Hyung
authors.initials: SH
authors.lastname: Park
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000213:Acyl Carrier Protein / Q000235:genetics*; D000935:Antifungal Agents / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D003001:Cloning, Molecular; D017353:Gene Deletion; D023061:Gene Order; D007783:Lactones / Q000378:metabolism; D008954:Models, Biological; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D048630:Polyketide Synthases / Q000235:genetics*; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D000213:Acyl Carrier Protein; D000935:Antifungal Agents; D007783:Lactones; C047787:neorustmicin A; C047784:rustmicin; D048630:Polyketide Synthases