Identification of a new oligomycin derivative as a specific inhibitor of the alternative peptidoglycan biosynthetic pathway.
Journal
The Journal of antibiotics
ISSN: 1881-1469
Titre abrégé: J Antibiot (Tokyo)
Pays: England
ID NLM: 0151115
Informations de publication
Date de publication:
10 Jan 2024
10 Jan 2024
Historique:
received:
14
07
2023
accepted:
19
11
2023
revised:
15
11
2023
medline:
11
1
2024
pubmed:
11
1
2024
entrez:
10
1
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38200161
doi: 10.1038/s41429-023-00693-0
pii: 10.1038/s41429-023-00693-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP23H02145
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP22H05130
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP22H04976
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP18H03937
Informations de copyright
© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.
Références
van Heijenoort J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat Prod Rep. 2001;18:503–19.
doi: 10.1039/a804532a
pubmed: 11699883
El Zoeiby A, Sanschagrin F, Levesque RC. Structure and function of the Mur enzymes: development of novel inhibitors. Mol Microbiol. 2003;47:1–12.
doi: 10.1046/j.1365-2958.2003.03289.x
pubmed: 12492849
Feng R, Satoh Y, Ogasawara Y, Yoshimura T, Dairi T. A glycopeptidyl-glutamate epimerase for bacterial peptidoglycan biosynthesis. J Am Chem Soc. 2017;139:4243–5.
doi: 10.1021/jacs.7b01221
pubmed: 28294606
Feng R, Satoh Y, Morita H, Ogasawara Y, Dairi T. Amino acid residues recognizing isomeric glutamate substrates in UDP-N-acetylmuramic acid-L-alanine-glutamate Synthetases. ACS Chem Biol. 2019;14:975–8.
doi: 10.1021/acschembio.9b00159
pubmed: 30977993
Ogasawara Y, et al. Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis. J Antibiot. 2020;73:125–7.
doi: 10.1038/s41429-019-0252-2
Fernandez-Chimeno RI, et al. IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation and biological activities. J Antibiot. 2000;53:474–8.
doi: 10.7164/antibiotics.53.474
Canedo LM, Fernandez-Puentes JL, Baz JP. IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. II. Physico-chemical properties and structure determination. J Antibiot. 2000;53:479–83.
doi: 10.7164/antibiotics.53.479
Lardy HA, Witonsky P, Johnson D. Antibiotics as Tools for Metabolic Studies. IV. Comparative Effectiveness of Oligomycins A, B, C, and Rutamycin as Inhibitors of Phosphoryl Transfer Reactions in Mitochondria. Biochemistry. 1965;4:552–4.
doi: 10.1021/bi00879a027
pubmed: 14311628