2. Academic Validation
  3. Identification of a new oligomycin derivative as a specific inhibitor of the alternative peptidoglycan biosynthetic pathway

Identification of a new oligomycin derivative as a specific inhibitor of the alternative peptidoglycan biosynthetic pathway

  • J Antibiot (Tokyo). 2024 Jan 10. doi: 10.1038/s41429-023-00693-0.
Shuhei Umetsu 1,  Takeshi Tsunoda 2,  Haruka Kiyanagi 1,  Yuki Inahashi 3,  Kenichi Nonaka 3,  Tohru Dairi 4,  Yasushi Ogasawara 5
Affiliations

Affiliations

  • 1 Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
  • 2 Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
  • 3 Ōmura Satoshi Memorial Institute, Kitasato University, Minato-ku, Tokyo, 108-8641, Japan.
  • 4 Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan. dairi@eng.hokudai.ac.jp.
  • 5 Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan. yogasawa@eng.hokudai.ac.jp.
PMID: 38200161 DOI: 10.1038/s41429-023-00693-0
Abstract

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.

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