Deletion of the accramycin pathway-specific regulatory gene accJ activates the production of unrelated polyketide metabolites

Fleurdeliz Maglangit* (Corresponding Author), Kwaku Kyeremeh, Hai Deng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

The manipulation of regulatory genes has been employed to awaken cryptic metabolites in Streptomyces. Of particular interest in recent years is the effect of disruption of a pathway-specific gene to other biosynthetic pathways. Herein, we report the inactivation of the accramycin pathway-specific regulatory gene, accJ in Streptomyces sp. MA37 resulted in the production of unrelated polyketide metabolites. Through detailed mass spectrometric and spectroscopic analyses, and comparison with literature data, their structures were deduced as 3-methoxy-2-methyl-4H-pyran-4-one (1), zanthopyranone (2), propioveratrone (3), and TW94a (4). To the best of our knowledge, this is the first report of the isolation of 1–3 from bacteria. Compounds 1, 2, and 4 showed weak to moderate activity against Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium. Propioveratrone (3) displayed better inhibitory activity (MIC = 6.3 μg/mL) than ampicillin against multi-drug resistant E. faecium K60–39 clinical isolate (MIC = 25 μg/mL), suggesting a promising structural template for the drug development targeting Enterococcus isolates.

Original languageEnglish
Pages (from-to)2753-2758
Number of pages6
JournalNatural Product Research
Volume37
Issue number16
Early online date20 Sept 2022
DOIs
Publication statusPublished - 1 Aug 2023

Bibliographical note

Funding
F.M. is thankful to the University of the Philippines (UP) Faculty, REPS and Administrative Staff Development Program (FRASDP), and the Department of Science and Technology (DOST) - National Research Council of the Philippines (NRCP) and the DOST-through the Science for Change Program (S4CP) Collaborative Research and Development to Leverage Philippine Economy (CRADLE) Project no. 8647. H.D. and K.K. are grateful to the Leverhulme Trust-Royal Society Africa award (AA090088) and UK Medical Research Council–UK Department for International Development (MRC/DFID) Concordat Agreement African Research Leaders Award (MR/S00520X/1).

Data Availability Statement

Supplementary data available at https://doi.org/10.6084/m9.figshare.21166201.v1

Keywords

  • Bioactivity
  • Enterococcus faecium
  • gene deletion
  • mutant
  • polyketides
  • Streptomyces

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