Biosynthesis of the Carbamoylated D ‐Gulosamine Moiety of Streptothricins: Involvement of a Guanidino‐ N ‐glycosyltransferase and an N ‐Acetyl‐ D ‐gulosamine Deacetylase

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.