Biosynthesis of the carbamoylated D-gulosamine moiety of streptothricins: involvement of a guanidino-N-glycosyltransferase and an N-acetyl-D-gulosamine deacetylase

Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5175-8. doi: 10.1002/anie.201412190. Epub 2015 Feb 26.

Abstract

Streptothricins (STNs) are atypical aminoglycosides containing a rare carbamoylated D-gulosamine (D-GulN) moiety, and the antimicrobial activity of STNs has been exploited for crop protection. Herein, the biosynthetic pathway of the carbamoylated D-GulN moiety was delineated. An N-acetyl-D-galactosamine is first attached to the streptolidine lactam by the glycosyltransferse StnG and then epimerized to N-acetyl-D-gulosamine by the putative epimerase StnJ. After carbamoylation by the carbamoyltransferase StnQ, N-acetyl-D-GulN is deacetylated by StnI to furnish the carbamoylated D-GulN moiety. In vitro studies characterized two novel enzymes: StnG is an unprecedented GT-A fold N-glycosyltransferase that glycosylates the imine nitrogen atom of guanidine, and StnI is the first reported N-acetyl-D-GulN deacetylase.

Keywords: D-gulosamine; aminoglycoside; biosynthesis; deacetylation; glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Carboxyl and Carbamoyl Transferases / metabolism*
  • Glycosylation
  • Glycosyltransferases / metabolism*
  • Multigene Family
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Streptomyces / genetics
  • Streptothricins / biosynthesis*
  • Streptothricins / chemistry
  • Streptothricins / pharmacology

Substances

  • Anti-Bacterial Agents
  • Streptothricins
  • Carboxyl and Carbamoyl Transferases
  • Glycosyltransferases