A stationary-phase acyl-coenzyme A synthetase of Streptomyces coelicolor A3(2) is necessary for the normal onset of antibiotic production
A stationary-phase acyl-coenzyme A synthetase of Streptomyces coelicolor A3(2) is necessary for the normal onset of antibiotic production
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DOI：
10.1128/aem.68.9.4240-4246.2002
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发表时间：
2002-09-01
影响因子：
4.4
通讯作者：
Gramajo, H
中科院分区：
文献类型：
--
作者：
Banchio, C;Gramajo, H
天蓝色链霉菌的 fadD1 和 macs1 基因是双基因操纵子的一部分。这两个基因都编码假定的酰基辅酶 A 合成酶 (ACS)。 FadD1 的氨基酸序列与几种 ACS 的氨基酸序列具有高度同源性，而 MACS1 与中链 ACS（广泛称为 SA 蛋白）具有最接近的同源性。与大肠杆菌的 FadD 一样，FadD1 也具有广泛的底物特异性，尽管饱和长链脂肪酸似乎是首选底物。 fadD1是一种生长阶段调控基因，其mRNA仅在生长稳定期检测到。有趣的是，fadD1 的突变会改变另一种 ACS 或 ACS 的水平，无论是在稳定期还是在指数生长期，至少当葡萄糖用作主要碳源时是这样。该突变体还表现出抗生素生产的严重缺陷，并且至少对于Act生物合成来说，这种缺陷似乎与Act生物合成基因的延迟表达有关。通过将 wt fadD1 等位基因引入细胞，抗生素的产生得以恢复，这证明了 ACS 活性与次级代谢物的生物合成之间的严格联系。这项研究的结果表明，ACS 可能是设计合理方法以提高抗生素产量的有用目标。
The fadD1 and macs1 genes of Streptomyces coelicolor are part of a two-gene operon. Both genes encode putative acyl coenzyme A synthetases (ACSs). The amino acid sequence of FadD1 has high homology with those of several ACSs, while MACS1 has the closest homology with medium-chain ACSs, broadly known as SA proteins. Like FadD of Escherichia coli, FadD1 also has a broad substrate specificity, although saturated long-chain fatty acids appears to be the preferred substrate. fadD1 is a growth-phase-regulated gene, and its mRNA is detected only during the stationary phase of growth. Interestingly, a mutation in fadD1 alters the levels of another ACS or ACSs, both at the stationary phase and at the exponential phase of growth, at least when glucose is used as a main carbon source. The mutant also shows a severe deficiency in antibiotic production, and at least for Act biosynthesis, this deficiency seems to be related to delayed expression of the Act biosynthetic genes. Antibiotic production is restored by the introduction of a wt fadD1 allele into the cell, demonstrating a strict link between ACS activity and the biosynthesis of secondary metabolites. The results of this study indicate that the ACSs may be useful targets for the design of rational approaches to improving antibiotic production.