Nanaomycin I and J: New nanaomycins generated by mycothiol-mediated compounds from "Streptomyces rosa subsp. notoensis" OS-3966

J Biosci Bioeng. 2019 May;127(5):549-553. doi: 10.1016/j.jbiosc.2018.10.013. Epub 2018 Nov 29.

Abstract

Two new nanaomycin analogs, nanaomycin I and J, were isolated from a cultured broth of an actinomycete strain, "Streptomyces rosa subsp. notoensis" OS-3966. In our previous study, we have confirmed the occurrence of nanaomycin I (m/z = 482 [M + H]+) that lacks a pseudo-disaccharide from the mycothiol of nanaomycin H under same culture condition. In this study, to confirm the structure of nanaomycin I, the strain "S. rosa subsp. notoensis" OS-3966 was re-cultured and the target compound with m/z = 482 [M + H]+ was isolated. Furthermore, we discovered another new analog, designated as nanaomycin J in isolating nanaomycin I. The NMR analyses revealed that the structures of nanaomycin I and J are N-acetylcysteine S-conjugates without a pseudo-disaccharide and N-acetylcysteine S-conjugates without a myo-inositol of nanaomycin H, respectively. The relative configurations of the tetrahydropyrane moiety of nanaomycin I and J were determined by rotating-frame overhauser effect spectroscopy (ROESY) analysis. Absolute configurations of the N-acetylcysteine moiety of nanaomycin I and J were determined by advanced Marfey's analyses for acid hydrolysis of de-sulfurized nanaomycin I and J with Raney nickel. Nanaomycin I and J showed moderate cytotoxicity against several human tumor cell lines.

Keywords: Actinomycete; Metabolite; Mycothiol; Nanaomycin I; Nanaomycin J; Streptomyces.

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / metabolism*
  • Cell Survival / drug effects
  • Cysteine / chemistry
  • Cysteine / metabolism*
  • Glycopeptides / chemistry
  • Glycopeptides / metabolism*
  • Humans
  • Inositol / chemistry
  • Inositol / metabolism*
  • Molecular Structure
  • Streptomyces / chemistry
  • Streptomyces / metabolism*

Substances

  • Anti-Infective Agents
  • Glycopeptides
  • mycothiol
  • Inositol
  • Cysteine