8-deoxy-rifamycin derivatives from amycolatopsis mediterranei S699 ∆rift strain

Feng Ye, Yanrong Shi, Shengliang Zhao, Zhiying Li, Haoxin Wang, Chunhua Lu, Yuemao Shen

Research output: Contribution to journalArticlepeer-review

Abstract

Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. In this study, the mutant strain Amycolatopsis mediterranei S699 ∆rifT was constructed by deleting the rifT gene. From this strain, eleven 8-deoxy-rifamycin derivatives (1–11) and seven known analogues (12–18) were isolated. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Compound 1 is a novel amide N-glycoside of seco-rifamycin. Compounds 2 and 3 feature conserved 11,12-seco-rifamycin W skeleton. The diverse post-modifications in the polyketide chain led to the production of 4–11. Compounds 2, 3, 5, 6, 13 and 15 exhibited antibacterial activity against Staphylococcus aureus (MIC (minimal inhibitory concentration) values of 10, 20, 20, 20, 40 and 20 µg/mL, respectively). Compounds 14, 15, 16, 17 and 18 showed potent antiproliferative activity against KG1 cells with IC50 (half maximal inhibitory concentration) values of 14.91, 44.78, 2.16, 18.67 and 8.07 µM, respectively.

Original languageEnglish (US)
Article number1265
Pages (from-to)1-14
Number of pages14
JournalBiomolecules
Volume10
Issue number9
DOIs
StatePublished - Sep 2020
Externally publishedYes

Keywords

  • Amycolatopsis mediterranei S699
  • Dehydrogenation
  • N-glycoside rifamycin
  • Proansamycin X
  • Rifamycin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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