Biosynthetic reconstitution of deoxysugar phosphoramidate metalloprotease inhibitors using an N-P-bond-forming kinase

Alexandra Baulig; Irina Helmle; Marius Bader; Felix Wolf; Andreas Kulik; Arwa Al-Dilaimi; Daniel Wibberg; Jörn Kalinowski; Harald Gross; Leonard Kaysser

doi:10.1039/c9sc00641a

Biosynthetic reconstitution of deoxysugar phosphoramidate metalloprotease inhibitors using an N-P-bond-forming kinase

Chem Sci. 2019 Mar 21;10(16):4486-4490. doi: 10.1039/c9sc00641a. eCollection 2019 Apr 28.

Authors

Alexandra Baulig^{1

2}, Irina Helmle¹, Marius Bader^{1

2}, Felix Wolf^{1

2}, Andreas Kulik³, Arwa Al-Dilaimi⁴, Daniel Wibberg⁴, Jörn Kalinowski⁴, Harald Gross^{1

2}, Leonard Kaysser^{1

2}

Affiliations

¹ Department of Pharmaceutical Biology , Pharmaceutical Institute , University of Tübingen , 72076 Tübingen , Germany . Email: [email protected].
² German Centre for Infection Research (DZIF) , partner site Tübingen , 72076 Tübingen , Germany.
³ Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT) , Microbiology/Biotechnology , University of Tübingen , 72076 Tübingen , Germany.
⁴ Center for Biotechnology (CeBiTec) , Bielefeld University , 33615 Bielefeld , Germany.

Abstract

Phosphoramidon is a potent metalloprotease inhibitor and a widespread tool in cell biology research. It contains a dipeptide backbone that is uniquely linked to a 6-deoxysugar via a phosphoramidate bridge. Herein, we report the identification of a gene cluster for the formation of phosphoramidon and its detailed characterization. In vitro reconstitution of the biosynthesis established TalE as a phosphoramidate-forming kinase and TalC as the glycosyltransferase which installs the l-rhamnose moiety by phosphoester linkage.