2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining
2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining
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DOI：
10.1073/pnas.0805530105
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发表时间：
2008-11-11
影响因子：
11.1
通讯作者：
Challis, Gregory L.
中科院分区：
文献类型：
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作者：
Corre, Christophe;Song, Lijiang;Challis, Gregory L.
生产抗生素亚甲霉素 (Mm) 及其调节所需的所有遗传元件都包含在 22 kb mmy-mmf 基因簇内，该基因簇位于天蓝色链霉菌 A3(2) 的 356 kb 线性质粒 SCP1 上。该基因簇内的 3 个基因的假定操纵子 mmfLHP 被提议指导 A 因子样信号分子的生物合成，该信号分子可以在 Mm 生物合成的调节中发挥作用。 mmfLHP 操纵子在 5. coelicolor M512（缺乏 SCP1 质粒的宿主，并且没有产生 prodiginine 和放线菌素抗生素的能力）中在其天然启动子的控制下表达。通过比较代谢分析，鉴定并阐明了 5 种新的 2-烷基-4-羟基甲基呋喃-3-羧酸 (AHFCA) 家族，统称为 Mm 呋喃 (MMF)，它们是 mmfLHP 基因的产物。 MMF 特异性诱导天蓝色链球菌产生 Mm 抗生素。比较基因组学分析和天然产物化学文献的检索表明，其他链霉菌可能产生 AHFCA，这表明它们可以在链霉菌物种中形成一类抗生素生物合成诱导剂，具有与更为人所知的 γ-丁内酯调节分子类似的功能。
All of the genetic elements necessary for the production of the antibiotic methylenomycin (Mm) and its regulation are contained within the 22-kb mmy-mmf gene cluster, which is located on the 356-kb linear plasmid SCP1 of Streptomyces coelicolor A3(2). A putative operon of 3 genes within this gene cluster, mmfLHP, was proposed to direct the biosynthesis of an A-factor-like signaling molecule, which could play a role in the regulation of Mm biosynthesis. The mmfLHP operon was expressed under the control of its native promoter in 5. coelicolor M512, a host lacking the SCP1 plasmid, and the ability to produce prodiginine and actinorhodin antibiotics. Comparative metabolic profiling led to the identification and structure elucidation of a family of 5 new 2-alkyl-4-hydroxymethyifuran-3-carboxylic acids (AHFCAs), collectively termed Mm furans (MMFs), as the products of the mmfLHP genes. MMFs specifically induce the production of the Mm antibiotics in S. coelicolor. Comparative genomics analyses and searches of the natural product chemistry literature indicated that other streptomycetes may produce AHFCAs, suggesting that they could form a general class of antibiotic biosynthesis inducers in Streptomyces species, with analogous functions to the better known gamma-butyrolactone regulatory molecules.