Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis.

Yasushi Ogasawara, Yohei Shimizu, Yohei Sato, Tomoki Yoneda, Yasuhide Inokuma, Tohru Dairi

The Journal of antibiotics 2020 Feb

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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.

Citation

Yasushi Ogasawara, Yohei Shimizu, Yohei Sato, Tomoki Yoneda, Yasuhide Inokuma, Tohru Dairi. Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis. The Journal of antibiotics. 2020 Feb;73(2):125-127