Merochlorins A-D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases.
Merochlorins A-D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases.
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DOI：
10.1021/ja305665f
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发表时间：
2012-07-25
影响因子：
15
通讯作者：
Moore BS
中科院分区：
文献类型：
--
作者：
Kaysser L;Bernhardt P;Nam SJ;Loesgen S;Ruby JG;Skewes-Cox P;Jensen PR;Fenical W;Moore BS
类萜化合物是一类具有广泛生物活性的聚酮-萜类混合天然产物。在此，我们提出了四个新的merochlorins A-D，由海洋细菌链霉菌属菌株CNH-189，具有新的化学骨架无关的已知细菌剂产生的merochlorins类抗生素的结构。基因组测序草案，诱变和异源生物合成的基因组最小化模式放线菌天蓝色链霉菌提供了一个57.6 kb的基因簇，其中包含两个基因编码罕见的细菌钒依赖性卤代过氧化物酶（VHPO）基因。两个不同的fosmid克隆的途径表达，其差异很大，VHPO基因mcl 40的存在或不存在，导致merochlorin C的差异生物合成，表明Mcl 40催化前所未有的15元氯诱导的大环化反应，将merochlorin D转化为merochlorin C。
Meroterpenoids are mixed polyketide-terpenoid natural products with a broad range of biological activities. Herein, we present the structures of four new meroterpenoid antibiotics, merochlorins A–D, produced by the marine bacterium Streptomyces sp. strain CNH-189, which possess novel chemical skeletons unrelated to known bacterial agents. Draft genome sequencing, mutagenesis and heterologous biosynthesis in the genome-minimized model actinomycete Streptomyces coelicolor provided a 57.6 kb gene cluster that contains two genes encoding rare bacterial vanadium-dependent haloperoxidase (VHPO) genes. Pathway expression of two different fosmid clones that differ largely by the presence or absence of the VHPO gene mcl40, resulted in the differential biosynthesis of merochlorin C, suggesting that Mcl40 catalyzes an unprecedented 15-membered chloronium-induced macrocyclization reaction converting merochlorin D to merochlorin C.