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.
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.
Karki
Suman
S
Department of Biological Science, Division of Bioscience and Bioinformatics, Myongji University, San 38-2 Nam-dong, Yongin-si, Gyunggi-do, Korea.
Kwon
So-Yeon
SY
Yoo
Hye-Gyeong
HG
Suh
Joo-Won
JW
Park
Si-Hyung
SH
Kwon
Hyung-Jin
HJ
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
D000213:Acyl Carrier Protein; D000935:Antifungal Agents; D007783:Lactones; C047787:neorustmicin A; C047784:rustmicin; D048630:Polyketide Synthases