Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase
Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase
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DOI：
10.1016/j.chembiol.2003.12.014
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
Shen, B
中科院分区：
文献类型：
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作者：
Tang, GL;Cheng, YQ;Shen, B
从 Streptomyces atroolivaceus S-140 中对包含 leinamycin (LNM) 生物合成基因簇的 135,638 bp DNA 区域进行了测序。 Inm 簇的边界是通过测序区域内开放阅读框的系统失活来定义的。 Inm 簇跨越 61.3 kb DNA，由 27 个编码非核糖体肽合成酶 (NRPS)、聚酮合酶 (PKS)、杂合 NRPS-PKS、抗性酶、调节酶和剪裁酶以及未知功能的蛋白质的基因组成。提出了 LNM 生物合成模型，其核心是 LNM 杂合 NRPS-PKS 大合成酶，由离散（LnmQ 和 LnmP）和模块化（Lnml）NRPS、无酰基转移酶的 PKS（LnmG、Lnml 和 LnmJ）以及具有不寻常结构域组织的 PKS 模块组成。这些研究揭示了 LNM 杂合 NRPS-PKS 巨合成酶前所未有的结构复杂性，并为研究 LNM 生物合成的分子基础奠定了基础。
A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140. The boundaries of the Inm cluster were defined by systematic inactivation of open reading frames within the sequenced region. The Inm cluster spans 61.3 kb of DNA and consists of 27 genes encoding nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), hybrid NRPS-PKS, resistance, regulatory, and tailoring enzymes, as well as proteins of unknown function. A model for LNM biosynthesis is proposed, central to which is the LNM hybrid NRPS-PKS megasynthetase consisting of discrete (LnmQ and LnmP) and modular (Lnml) NRPS, acyltransferase-less PKS (LnmG, Lnml, and LnmJ), and PKS modules with unusual domain organization. These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis.