C-glycosylation of anhydrotetracycline scaffold with SsfS6 from the SF2575 biosynthetic pathway

J Antibiot (Tokyo). 2014 Jan;67(1):65-70. doi: 10.1038/ja.2013.88. Epub 2013 Sep 11.

Abstract

Glycosylation with deoxysugar is a common strategy used by nature to introduce structural diversity and biological activities among natural products. In this study, we biochemically confirmed the activities of SsfS6, a C-glycosyltransferase in the SF2575 biosynthetic pathway, as a regioselective D-olivose transferase that acts on the C-9 position of an anhydrotetracycline aglycon. To perform the glycosyl transfer reaction using Escherichia coli as a whole-cell biocatalyst, we reconstituted the biosynthesis of TDP-D-olivose using a heterologous pathway. Under in vivo conditions, SsfS6 transferred multiple endogenous sugar substrates, in addition to D-olivose, to the anhydrotetracycline substrate, demonstrating broad substrate tolerance and potential as a tetracycline-diversifying enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Deoxy Sugars / biosynthesis*
  • Escherichia coli / metabolism*
  • Glycosylation
  • Glycosyltransferases / metabolism*
  • Tetracyclines / biosynthesis*
  • Tetracyclines / chemistry

Substances

  • Deoxy Sugars
  • Tetracyclines
  • SF 2575
  • 4-epianhydrotetracycline
  • olivose
  • Glycosyltransferases