文章基本信息

标题：Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis
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作者：Haruo Ikeda ; Tomoko Nonomiya ; Masayo Usami 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：17
页码：9509-9514
DOI：10.1073/pnas.96.17.9509
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large ORFs encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3, and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 homologous sets of enzyme activities (modules), each catalyzing a specific round of polyketide chain elongation. The clustered genes encoding polyketide synthase are organized as two sets of six modular repeats, aveA1-aveA2 and aveA3-aveA4, which are convergently transcribed. The total of 55 constituent active sites makes this the most complex multifunctional enzyme system identified to date. The sequenced DNA region contains 14 additional ORFs, some of which encode polypeptides governing other key steps in avermectin biosynthesis. Between the two sets of polyketide synthase genes lie two genes involved in postpolyketide modification, one of which encodes cynthochrome P450 hydroxylase that probably catalyzes furan ring formation at C6 to C8a. Immediately right of the large polyketide synthase genes is a set of genes involved in oleandrose biosynthesis and its transglycosylation to polyketide-derived aglycons. This cluster includes nine genes, but one is not functional in the biosynthesis of avermectin. On the left side of polyketide synthase genes, two ORFs encoding methyltransferase and nonpolyketide synthase ketoreductase involved in postpolyketide modification are located to the left of the polyketide synthase genes, and an adjacent gene encodes a regulatory function that may be involved in activation of the transcription of avermectin biosynthetic genes.