Systematic unravelling of the biosynthesis of poly (L-diaminopropionic acid) in Streptomyces albulus PD-1.
Systematic unravelling of the biosynthesis of poly (L-diaminopropionic acid) in Streptomyces albulus PD-1.
复制标题
系统阐明白色链霉菌 PD-1 中聚（L-二氨基丙酸）的生物合成
DOI：
10.1038/srep17400
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发表时间：
2015-12-03
影响因子：
4.6
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Xu Z;Sun Z;Li S;Xu Z;Cao C;Xu Z;Feng X;Xu H
聚l -二氨基丙酸（PDAP）是在自然界中发现的四种均聚氨基酸之一。然而，PDAP生物合成的分子机制尚不清楚。本研究通过基因组挖掘、基因破坏、异源表达和体外饲养实验，对白链霉菌PD-1中PDAP生物合成途径的总体布局进行了表征。结果表明，作为PDAP单体的l -二氨基丙酸（L-DAP）是由半胱氨酸合成酶和鸟氨酸环脱氨酶的两个蛋白同源物共同合成的。然后，L-DAP通过具有经典腺苷化和肽基载体蛋白结构域的新型非核糖体肽合成酶（NRPS）组装成PDAP。然而，与传统的NRPS的缩合结构域或硫酯酶结构域不同，该NRPS在c端有7个跨膜结构域围绕3个串联可溶性结构域。据我们所知，这种新的单模NRPS结构只在聚ε- l -赖氨酸合成酶中报道过。PDAP合成酶与聚ε- l -赖氨酸合成酶具有相似的NRPS结构，这可能是均聚氨基酸合成酶的共同特征。在这种情况下，我们可能会在未来通过挖掘这种新的NRPS结构来发现和/或设计更多的同源（氨基酸）。
Poly(L-diaminopropionic acid) (PDAP) is one of the four homopoly(amino acid)s that have been discovered in nature. However, the molecular mechanism of PDAP biosynthesis has yet to be described. In this work, the general layout of the PDAP biosynthetic pathway is characterised in Streptomyces albulus PD-1 by genome mining, gene disruption, heterologous expression and in vitro feeding experiments. As a result, L-diaminopropionic acid (L-DAP), which is the monomer of PDAP, is shown to be jointly synthesised by two protein homologues of cysteine synthetase and ornithine cyclodeaminase. Then, L-DAP is assembled into PDAP by a novel nonribosomal peptide synthetase (NRPS) with classical adenylation and peptidyl carrier protein domains. However, instead of the traditional condensation or thioesterase domain of NRPSs, this NRPS has seven transmembrane domains surrounding three tandem soluble domains at the C-terminus. As far as we know, this novel single-module NRPS structure has only been reported in poly(ε-L-lysine) synthetase. The similar NRPS structure of PDAP synthetase and poly(ε-L-lysine) synthetase may be a common characteristic of homopoly(amino acid)s synthetases. In this case, we may discover and/or design more homopoly(amino acid)s by mining this kind of novel NRPS structure in the future.