ε-Poly-L-lysine dispersity is controlled by a highly unusual nonribosomal peptide synthetase
ε-Poly-L-lysine dispersity is controlled by a highly unusual nonribosomal peptide synthetase
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DOI：
10.1038/nchembio.125
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发表时间：
2008-12-01
影响因子：
14.8
通讯作者：
Hamano, Yoshimitsu
中科院分区：
文献类型：
--
作者：
Yamanaka, Kazuya;Maruyama, Chitose;Hamano, Yoshimitsu
ε-聚-L-赖氨酸（ε-PL）由异肽键中的25-35个L-赖氨酸残基组成，并且是自然界中已知的仅有的两种氨基酸均聚物之一。阐明epsilon-PL的生物合成机制应该为创造新型生物聚合物开辟新的途径。在这里，我们报告的ε-PL合成酶（PLS; 130 kDa）的纯化和克隆其基因从ε-PL产生菌株的白色链霉菌。Pls是一种膜蛋白，具有非核糖体肽合成酶（NRPS）的特征性腺苷酸化和巯基化结构域。它没有传统的缩合或硫酯酶结构域;相反，它有六个跨膜结构域围绕三个串联的可溶性结构域。这些串联结构域使用游离L-赖氨酸聚合物（或初始反应中的单体）作为受体和Pls结合的L-赖氨酸作为供体反复催化L-赖氨酸聚合，直接产生不同长度的链。因此，Pls是一种新的单模块NRPS，具有氨基酸连接酶样催化活性的肽键形成。
epsilon-Poly-L-lysine (epsilon-PL) consists of 25-35 L-lysine residues in isopeptide linkages and is one of only two amino acid homopolymers known in nature. Elucidating the biosynthetic mechanism of epsilon-PL should open new avenues for creating novel classes of biopolymers. Here we report the purification of an epsilon-PL synthetase (Pls; 130 kDa) and the cloning of its gene from an epsilon-PL-producing strain of Streptomyces albulus. Pls was found to be a membrane protein with adenylation and thiolation domains characteristic of the nonribosomal peptide synthetases (NRPSs). It had no traditional condensation or thioesterase domain; instead, it had six transmembrane domains surrounding three tandem soluble domains. These tandem domains iteratively catalyzed L-lysine polymerization using free L-lysine polymer (or monomer in the initial reaction) as acceptor and Pls-bound L-lysine as donor, directly yielding chains of diverse length. Thus, Pls is a new single-module NRPS having an amino acid ligase-like catalytic activity for peptide bond formation.