Exploring peptide ligase orthologs in actinobacteria-discovery of pseudopeptide natural products, ketomemicins-
Exploring peptide ligase orthologs in actinobacteria-discovery of pseudopeptide natural products, ketomemicins-
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探索放线菌中的肽连接酶直系同源物-伪肽天然产物酮霉素的发现-
DOI：
10.1021/acschembio.6b00046
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发表时间：
2016
期刊：
影响因子：
4
通讯作者：
and T. Dairi
中科院分区：
文献类型：
--
作者：
Y. Ogasawara;J. Kawata;M. Noike;Y. Satoh;K. Furihata;and T. Dairi
我们最近发现了一种新的肽连接酶（PGM1），一种atp -抓住连接酶，它催化(S)-2-（3,5-二羟基-4-甲氧基苯基）-2-胍乙酸和核糖体提供的寡肽之间的酰胺键形成。这是利用多肽作为亲核试剂的atp抓握连接酶的第一个例子。为了探索这种酶的潜力，我们进行了BLAST搜索并确定了许多同源物。mobarastreptomomyces，Salinispora tropica和micromonosporasp的直系同源物。在由6个基因组成的相似基因簇中发现。为了探究这些基因的功能，我们异种表达了每一个基因簇，并在所有转化子的肉汤中检测到新的和结构相似的假三肽。此外，一个重组的PGM1同源的小单孢子虫。被证明是一种新型的二肽连接酶，可催化氨基精氨酸与二肽之间形成酰胺键，生成三肽；这是首次报道利用二肽作为亲核试剂的肽连接酶。
We recently identified a novel peptide ligase (PGM1), an ATP-grasp-ligase, that catalyzes amide bond formation between (S)-2-(3,5-dihydroxy-4-methoxyphenyl)-2-guanidinoacetic acid and ribosomally supplied oligopeptides in pheganomycin biosynthesis. This was the first example of an ATP-grasp-ligase utilizing peptides as nucleophiles. To explore the potential of this type of enzyme, we performed a BLAST search and identified many orthologs. The orthologs ofStreptomyces mobaraensis,Salinispora tropica, andMicromonosporasp. were found in similar gene clusters consisting of six genes. To probe the functions of these genes, we heterologously expressed each of the clusters inStreptomyces lividansand detected novel and structurally similar pseudotripeptides in the broth of all transformants. Moreover, a recombinant PGM1 ortholog ofMicromonosporasp. was demonstrated to be a novel dipeptide ligase catalyzing amide bond formation between amidino-arginine and dipeptides to yield tripeptides; this is the first report of a peptide ligase utilizing dipeptides as nucleophiles.