Banchio C, Gramajo H
Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
Appl Environ Microbiol. 2002 Sep;68(9):4240-6. doi: 10.1128/AEM.68.9.4240-4246.2002.
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.
天蓝色链霉菌的fadD1和macs1基因是一个双基因操纵子的组成部分。这两个基因都编码推定的酰基辅酶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具有最密切的同源性，中链ACS通常被称为SA蛋白。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是一个生长阶段调控基因，其mRNA仅在生长的稳定期被检测到。有趣的是，fadD1中的突变会改变另一种或多种ACS在生长稳定期和指数期的水平，至少在以葡萄糖作为主要碳源时是这样。该突变体在抗生素生产方面也表现出严重缺陷，至少对于放线菌素生物合成来说，这种缺陷似乎与放线菌素生物合成基因的表达延迟有关。通过将野生型fadD1等位基因导入细胞，抗生素生产得以恢复，这表明ACS活性与次级代谢产物的生物合成之间存在紧密联系。这项研究的结果表明，ACS可能是设计合理方法来提高抗生素产量的有用靶点。
