Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida
Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida
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DOI：
10.1016/s0378-1097(02)01123-0
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发表时间：
2003-01-21
影响因子：
2.1
通讯作者：
Kato, F
中科院分区：
文献类型：
--
作者：
Anzai, Y;Salto, N;Kato, F
霉素是由灰红小单孢菌A11725产生的一种16元大环内酯类抗生素，由一个支链内酯和两个位于C-5和C-21位的糖（desosamine和mycinose）组成，对革兰氏阳性菌具有很强的抗菌活性。完整测定了该基因簇的核苷酸序列（62 kb），其中有22个开放阅读框（ORF）。来自22个ORF的所有产物都负责生物合成mycinamicin II和对合成的化合物的自我保护。该簇的中心是一个聚酮合酶基因座（mycA），它编码一个由五个多功能蛋白组成的七模块系统。紧接着mycA的下游，有一组用于desosamine生物合成的基因（mydA-G和mycB）。此外，mydH位于mydA和B之间，其产物负责霉素糖的生物合成。另一方面，在霉素PKS基因上游检测到8个ORF。MyrB、mycG和mycF基因已经由Inouye等人鉴定。其他五个ORF（mycCI、mycCII、mydI、mycE和myeD）位于myeAl和mycF之间，并且这五个基因和mycF负责霉素糖的生物合成。在PKS基因中，模块1、4、5和6中的KS和AT结构域的四个区域表明它不显示链霉菌基因典型的高GC含量，也不显示链霉菌基因的不寻常的框架图模式。甲基丙二酰辅酶A被用作这四个模块的功能单元中的底物。在其他的PKS基因中，KS和AT结构域的框架图模式与底物的关系也被观察到，这表明KS-AT起始区被水平转移到了几个放线菌菌株染色体DNA上的PKS基因中。(C)2002年由Elsevier Science B. V.代表欧洲微生物学会联合会出版。
Mycinamicin, composed of a branched lactone and two sugars, desosamine and mycinose, at the C-5 and C-21 positions, is a 16-membered macrolide antibiotic produced by Micromonospora griseorubida A11725, which shows strong antimicrobial activity against Gram positive bacteria. The nucleotide sequence (62 kb) of the mycinamicin biosynthetic gene cluster, in which there were 22 open reading frames (ORFs), was completely determined. All of the products from the 22 ORFs are responsible for the biosynthesis of mycinamicin II and self-protection against the compounds synthesized. Central to the cluster is a polyketide synthase locus (mycA), which encodes a seven-module system comprised of five multifunctional proteins. Immediately downstream of mycA, there is a set of genes for desosamine biosynthesis (mydA-G and mycB). Moreover, mydH, whose product is responsible for the biosynthesis of mycinose, lies between mydA and B. On the other hand, eight ORFs were detected upstream of the mycinamicin PKS gene. The myrB, mycG, and mycF genes had already been characterized by Inouye et al. The other five ORFs (mycCI, mycCII, mydI, mycE, and myeD) lie between myeAl and mycF, and these five genes and mycF are responsible for the biosynthesis of mycinose. In the PKS gene, four regions of KS and AT domains in modules 1, 4, 5, and 6 indicated that it does not show the high GC content typical for Streptomyces genes, nor the unusual frame plot patterns for Streptomyces genes. Methylmalonyl-CoA was used as substrate in the functional units of those four modules. The relationship between the substrate and the unusual frame plot pattern of the KS and AT domains was observed in the other PKS genes, and it is suggested that the KS-AT original region was horizontally transferred into the PKS genes on the chromosomal DNA of several actinomycetes strains. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.