Journal
FEMS MICROBIOLOGY LETTERS
Volume 310, Issue 1, Pages 69-75Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1574-6968.2010.02048.x
Keywords
galbonolide A; methoxymalonyl-acyl carrier protein; Streptomyces galbus; antifungal compound; polyketide synthase
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Funding
- Korean Government (MOEHRD) [KRF-2008-331-C00244, 2009-0074283]
- Rural Development Administration, Korea [20070401-034023]
- National Research Foundation of Korea [2009-0074283] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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