3-hydroxy-3-methylglutaryl-CoA-like synthases direct the formation of methyl and ethyl side groups in the biosynthesis of the antibiotic myxovirescin A
3-hydroxy-3-methylglutaryl-CoA-like synthases direct the formation of methyl and ethyl side groups in the biosynthesis of the antibiotic myxovirescin A
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DOI：
10.1002/cbic.200700017
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发表时间：
2007-03-26
期刊：
影响因子：
3.2
通讯作者：
Mueller, Rolf
中科院分区：
文献类型：
--
作者：
Simunovic, Vesna;Mueller, Rolf
方案1. A）编码单功能酶的粘病毒素A生物合成基因簇的10.9-kb片段。TaB和TaE是HMG-CoA合酶的推定ACP、TaC和TaF同源物，TaK是突变的β-酮脂酰-ACP合酶（KSS），TaX和TaY是烯酰-CoA水合酶的巴豆酸酶家族的同源物。B）粘病毒素A（1）的结构，表明其构建单元的生物合成来源。[10加框的碳源自甘氨酸，黑色圆圈表示乙酸酯的C2，三角形表示源自甲硫氨酸的甲基，连接的正方形表示源自琥珀酸酯的碳2和3的乙基。C）基于参考文献的粘病毒素A组装的工作模型，[6，7，11]描述了涉及HMG样和ECH酶同系物的两轮修饰反应，其发生在聚酮化合物/非核糖体肽中间体2，3，5和6上。由taV编码的两种AT将丙二酰-CoA（M-CoA）和甲基丙二酰-CoA（Mm-CoA）装载到其同源ACP（TaB和TaE）上，其成为脱羧酶TaK的底物。乙酰基-S-TaB和丙酰基-S-TaE分别作为TaC和TaF HMG样内切酶的第二底物。碳标记模式描述于（B）中。推测中间体7的C16-C17双键被TaO PKS还原。
Scheme 1. A) 10.9-kb fragment of the myxovirescin A biosynthetic gene cluster encoding for monofunctional enzymes. TaB and TaE are putative ACPs, TaC and TaF homologues of HMG-CoA synthases, TaK is a mutant β-ketoacyl-ACP synthase (KSS), and TaX and TaY are homologues of the crotonase family of enoyl-CoA hydratases. B) Structure of myxovirescin A (1) indicating the biosynthetic origin of its building units.[10 Boxed carbons originate from glycine, black circles indicate C2 of acetate, triangles indicate methyl groups derived from methionine, and connected squares show the ethyl group originating from carbons 2 and 3 of succinate. C) A working model of myxovirescin A assembly, based on refs.,[6, 7, 11] depicts two rounds of modification reactions involving HMGS-like and ECH enzyme homologues taking place on the polyketide/nonribosomal peptide intermediates 2, 3, 5 and 6. Two ATs encoded by taV load malonyl-CoA (M-CoA) and methylmalonyl-CoA (Mm-CoA) onto their cognate ACPs (TaB and TaE), which become substrates of the decarboxylase TaK. Acetyl-S-TaB and propionyl-S-TaE serve as second substrates for TaC and TaF HMGS-like synthases, respectively. The carbon-labelling pattern is described in (B). The C16 C17 double bond of intermediate 7 is presumably reduced by TaO PKS.