Discovery and structure elucidation of glycosyl and 5-hydroxy migrastatins from dung beetle gut Kitasatospora sp

J Ind Microbiol Biotechnol. 2023 Feb 17;50(1):kuad046. doi: 10.1093/jimb/kuad046.

Abstract

Two new macrocyclic secondary metabolites, glycosyl-migrastatin (1) and 5-hydroxy-migrastatin (2), were isolated from a gut bacterium Kitasatospora sp. JL24 in dung beetle Onthophagus lenzii. Based on a comprehensive analysis of the nuclear magnetic resonance (NMR), MS, and UV spectroscopic data, the planar structures of 1 and 2 were successfully identified as new derivatives of migrastatin. Compound 1 was the first glycosylated member of the migrastatin family. The absolute configuration of the sugar moiety was determined to be d-glucose through the analysis of coupling constants and ROESY correlations, followed by chemical derivatization and chromatographic comparison with authentic d- and l-glucose. Compound 2, identified as 5-hydroxy-migrastatin possessing an additional hydroxy group with a previously unreported chiral center, was assigned using Mosher's method through 19F NMR chemical shifts and confirmed with the modified Mosher's method. Genomic analysis of Kitasatospora sp. strain JL24 revealed a putative biosynthetic pathway involving an acyltransferase-less type I polyketide synthase biosynthetic gene cluster.

One-sentence summary: Two secondary metabolites, glycosyl-migrastatin (1) and 5-hydroxy-migrastatin (2), were discovered from the gut bacterium Kitasatospora sp. JL24 in the dung beetle Onthophagus lenzii.

Keywords: Kitasatospora sp; Biosynthetic pathway; Insect gut bacteria; Macrocyclic lactone; Migrastatin; Secondary metabolites.

MeSH terms

  • Bacteria
  • Macrolides*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Piperidones*

Substances

  • migrastatin
  • Glucose, (L)-Isomer
  • Macrolides
  • Piperidones