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Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis.
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2019-10-25 , DOI: 10.1038/s41429-019-0252-2
Yasushi Ogasawara 1 , Yohei Shimizu 2 , Yohei Sato 2 , Tomoki Yoneda 1 , Yasuhide Inokuma 1 , Tohru Dairi 1
Affiliation  

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.

中文翻译:

放线菌素D鉴定为肽聚糖生物合成替代途径的特异性抑制剂。

肽聚糖是细菌细胞壁必不可少的成分。我们最近发现了另一种肽聚糖生物合成途径,该途径涉及两种酶MurD2和MurL,分别催化L-Glu与UDP-MurNAc-L-Ala的连接和MurD2产物的末端L-Glu的差向异构化。由于该途径在引起水稻细菌性枯萎病的病原体黄单胞菌(Xanthomonas oryze)中起作用,因此我们从放线菌产生的代谢产物中搜索了特定的抑制剂,从而获得了用作农药的先导化合物。从小链霉菌NBRC 13193中分离出放线菌素D作为该途径的特异性抑制剂。体外分析表明放线菌素D抑制了MurD2反应。
更新日期:2020-01-16
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