Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
J Antibiot (Tokyo). 2024 Mar;77(3):182-184. doi: 10.1038/s41429-023-00693-0. Epub 2024 Jan 10.
Peptidoglycan is an important macromolecule in bacterial cell walls to maintain cell integrity, and its biosynthetic pathway has been well studied. Recently, we demonstrated that some bacteria such as Xanthomonas oryzae, a pathogen causing bacterial blight of rice, used an alternative pathway for peptidoglycan biosynthesis. In this pathway, MurD2, a MurD homolog, catalyzed the attachment of L-Glu to UDP-MurNAc-L-Ala and MurL, which did not show homology to any known protein, catalyzed epimerization of the terminal L-Glu of the MurD2 product to generate UDP-MurNAc-L-Ala-D-Glu. Because the alternative pathway also operates in some other plant pathogens and opportunistic pathogens, specific inhibitors of the alternative pathway could function as pesticides and antibiotics for these pathogens. In this study, we searched for specific inhibitors of the alternative pathway from metabolites produced by actinomycetes and identified a new oligomycin-class polyketide, which was revealed to inhibit the MurD2 reaction, in culture broth of Micromonospora sp. K18-0097.
肽聚糖是细菌细胞壁中的一种重要大分子物质，用于维持细胞完整性，其生物合成途径已得到充分研究。最近，我们证明了一些细菌，如引起水稻细菌性条斑病的稻黄单胞菌，使用了一种替代的肽聚糖生物合成途径。在这个途径中，MurD2，一种 MurD 同源物，催化 L-Glu 与 UDP-MurNAc-L-Ala 和 MurL 的连接，而 MurL 与任何已知的蛋白质都没有同源性，催化 MurD2 产物末端 L-Glu 的差向异构化，生成 UDP-MurNAc-L-Ala-D-Glu。由于替代途径也在一些其他植物病原体和机会性病原体中起作用，因此替代途径的特异性抑制剂可以作为这些病原体的农药和抗生素。在这项研究中，我们从放线菌产生的代谢物中寻找替代途径的特异性抑制剂，并从 Micromonospora sp. K18-0097 的发酵液中鉴定出一种新的寡霉素类聚酮化合物，它被证明可以抑制 MurD2 反应。
