The methoxymalonyl-acyl carrier protein biosynthesis locus and the nearby gene with the β-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
The methoxymalonyl-acyl carrier protein biosynthesis locus and the nearby gene with the β-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
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DOI：
10.1111/j.1574-6968.2010.02048.x
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发表时间：
2010-09-01
影响因子：
2.1
通讯作者：
Kwon, Hyung-Jin
中科院分区：
文献类型：
--
作者：
Karki, Suman;Kwon, So-Yeon;Kwon, Hyung-Jin
Galbonolides A和B是抗真菌化合物，由Streptomyces galbus产生。一个多模块聚酮合酶（PKS）被预测催化它们的生物合成，并且一个甲氧基丙二酰-酰基载体蛋白（甲氧基丙二酰-ACP）被预测参与半乳糖苷A的生物合成。甲氧丙二酰-ACP生物合成位点（galGHIJK）及其侧翼区的克隆揭示了该位点与β-酮脂酰合酶（KAS）相关基因（orf 3、4和5）共定位，但与S. galbus。galI-破坏突变体（SK-galI-5）不能产生galbonectin A，但可以合成galbonectin B，表明galGHIJK参与galbonectin A的生物合成。orf 4的破坏突变体在产生糖内酯A和B两者中严重受损。这些结果表明，galGHIJK和KAS基因参与的galbonolides的生物合成，虽然他们不是共定位的多模块PKS基因簇。我们进一步提出，一个单一的galbonolide PKS产生两个离散的结构，galbonolides A和B，通过交替纳入甲氧基丙二酸酯和甲基丙二酸酯，分别。
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.