Geistlich M, Losick R, Turner J R, Rao R N
Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138.
Mol Microbiol. 1992 Jul;6(14):2019-29. doi: 10.1111/j.1365-2958.1992.tb01374.x.
A key step in the biosynthesis of macrolide antibiotics is the assembly of a large macrocyclic lactone ring by a multienzyme protein complex called the polyketide synthase. In the species Streptomyces ambofaciens, the polyketide synthase for the assembly of the 16-membered ring of the macrolide antibiotic spiramycin is encoded by the biosynthetic gene srmG. Here we show that the accumulation of transcripts from the srmG promoter is governed by the regulatory gene srmR, whose predicted product, a 65 kDa polypeptide, is not significantly similar in its deduced amino acid sequence to that of previously reported proteins in the protein databases. The srmR gene product is also required for the accumulation of transcripts from srmX, an additional gene in the vicinity of srmR, but not for the accumulation of transcripts from srmR itself. Interestingly, mutations in srmR prevent the accumulation of transcripts from the spiramycin resistance gene srmB, but this is an indirect consequence of the failure of srmR mutants to produce spiramycin, which is an inducer of its own resistance gene. The possibility that srmR is the prototype for a new class of regulatory genes governing early events in the biosynthesis of macrolide antibiotics is discussed.
大环内酯类抗生素生物合成中的关键步骤是由一种称为聚酮合酶的多酶蛋白复合物组装一个大的大环内酯环。在产二素链霉菌中，用于组装大环内酯类抗生素螺旋霉素16元环的聚酮合酶由生物合成基因srmG编码。我们在此表明，来自srmG启动子的转录本积累受调控基因srmR控制，其预测产物是一种65 kDa的多肽，在推导的氨基酸序列上与蛋白质数据库中先前报道的蛋白质没有显著相似性。srmR基因产物对于来自srmX（srmR附近的另一个基因）的转录本积累也是必需的，但对于来自srmR自身的转录本积累则不是必需的。有趣的是，srmR中的突变会阻止来自螺旋霉素抗性基因srmB的转录本积累，但这是srmR突变体无法产生螺旋霉素的间接后果，螺旋霉素是其自身抗性基因的诱导物。本文讨论了srmR作为控制大环内酯类抗生素生物合成早期事件的一类新调控基因原型的可能性。
