Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis
Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis
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DOI：
10.1038/s41429-019-0252-2
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发表时间：
2020-02-01
影响因子：
3.3
通讯作者：
Dairi, Tohru
中科院分区：
文献类型：
--
作者：
Ogasawara, Yasushi;Shimizu, Yohei;Dairi, Tohru
肽聚糖是细菌细胞壁不可缺少的组成部分。我们最近发现了一种替代的肽聚糖生物合成途径，其涉及两种酶，MurD 2和MurL，分别催化I-Glu与UDP-MurNAc-I-Ala的连接和MurD 2产物的末端I-Glu的差向异构化。由于该途径在引起水稻白叶枯病的病原体水稻黄单胞菌中起作用，我们从放线菌产生的代谢产物中寻找特异性抑制剂，以获得作为农用化学品的先导化合物。放线菌素D是从小链霉菌NBRC 13193中分离出来的一种特异性抑制剂。体外分析表明，放线菌素D抑制MurD 2反应。
Peptidoglycan is an indispensable component of bacterial cell walls. We recently discovered an alternative peptidoglycan biosynthetic pathway, which involves two enzymes, MurD2 and MurL, catalyzing the ligation of l-Glu to UDP-MurNAc-l-Ala and epimerization of the terminal l-Glu of the MurD2 product, respectively. Because the pathway operates in Xanthomonas oryze, a pathogen causing bacterial blight of rice, we searched for specific inhibitors from metabolites produced by actinomycetes to obtain a lead compound to function as an agrochemical. Actinomycin D was isolated from Streptomyces parvulus NBRC 13193 as a specific inhibitor of the pathway. In vitro analysis indicated that actinomycin D inhibited the MurD2 reaction.