Mutasynthesis of enterocin and wailupemycin analogues
Mutasynthesis of enterocin and wailupemycin analogues
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DOI：
10.1021/ja035973o
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发表时间：
2003-08-06
影响因子：
15
通讯作者：
Moore, BS
中科院分区：
文献类型：
--
作者：
Kalaitzis, JA;Izumikawa, M;Moore, BS
新型苯丙氨酸解氨酶基因encP（其产物是海洋链霉菌细菌苯甲酰辅酶A（CoA）生物合成途径的关键组成部分）失活，导致苯甲酸酯引发的聚酮化合物肠菌素和瓦卢佩霉素G的生产丧失。施用了一系列肉桂酸酯和苯甲酸酯衍生物 ΔencP突变体，导致形成带有对氟苯甲酸酯、2-和3-噻吩甲酸酯以及环己-1-烯甲酸酯残基的新型类似物。鉴于苯甲酸酯：CoA 连接酶 EncN 被评估为对芳基酸具有广泛的体外底物特异性，体内观察到的严格起始单元特异性表明肠菌素 II 型聚酮合酶 (PKS) 对起始单元的选择发挥选择性控制。这项研究代表了第一个迭代 II 型 PKS 突变合成实验。
Inactivation of the novel phenylalanine ammonia lyase geneencP, whose product is a key component in the biosynthetic pathway to benzoyl-coenzyme A (CoA) in the bacteriumStreptomyces maritimus, resulted in the loss of production of the benzoate-primed polyketides enterocin and wailupemycin G. A series of cinnamate and benzoate derivatives were administered to the ΔencPmutant, resulting in the formation of novel analogues bearingp-fluorobenzoate, 2- and 3-thiophenecarboxylate, and cyclohex-1-enecarboxylate residues. Given that the benzoate:CoA ligase EncN was evaluated to have broad in vitro substrate specificity towards aryl acids, the strict starter unit specificity observed in vivo indicates that the enterocin type II polyketide synthase (PKS) exerts selective control over the choice of starter units. This study represents the first mutasynthesis experiments with iterative type II PKSs.