Ravidomycin Analogs from Streptomyces sp. Exhibit Altered Antimicrobial and Cytotoxic Selectivity

  • J Nat Prod. 2023 Aug 25;86(8):1968-1979. doi: 10.1021/acs.jnatprod.3c00381.
Kyoung Jin Park  1 ,  Sarah Maier  1 ,  Chengqian Zhang  1 ,  Shelley A H Dixon  2 ,  Douglas B Rusch  3 ,  Monica T Pupo  4 ,  Steven P Angus  2 ,  Joseph P Gerdt  1
Affiliations
  • 1. Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.
  • 2. Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
  • 3. Center for Genomics and Bioinformatics, Indiana University, Bloomington, Indiana 47405, United States.
  • 4. School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Ribeirao Preto, São Paulo 05508-220, Brazil.
PMID: 37531219 DOI: 10.1021/acs.jnatprod.3c00381
Abstract

Six new ravidomycin analogs (1-4, 6, and 7) were isolated from Streptomyces sp. Am59 using UV- and LCMS-guided separation based on Global Natural Products Social (GNPS) molecular networking analysis. Furthermore, we isolated fucomycin V (9), which possesses the same chromophore as ravidomycin but features a d-fucopyranose instead of d-ravidosamine. This is the first report of 9 as a natural product. Four new analogs (10-13) of 9 were also isolated. The structures were elucidated by combined spectroscopic and computational methods. We also found an inconsistency with the published [α]D25 of deacetylravidomycin, which is reported to have a (-) sign. Instead, we observed a (+) specific rotation for the reported absolute configuration of deacetylravidomycin (containing d-ravidosamine). We confirmed the positive sign by reisolating deacetylravidomycin from S. ravidus and by deacetylating ravidomycin. Finally, Antibacterial, Antifungal, and cytotoxicity activities were determined for the compounds. Compared to deacetylravidomycin, the compounds 4-6, 9, 11, and 12 exhibited greater Antibacterial selectivity.

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