Conversion of a Disulfide Bond into a Thioacetal Group during Echinomycin Biosynthesis1. (2nd December 2013)

• Record Type: Journal Article
• Authors: Hotta, Kinya; Keegan, Ronan M.; Ranganathan, Soumya; Fang, Minyi; Bibby, Jaclyn; Winn, Martyn D.; Sato, Michio; Lian, Mingzhu; Watanabe, Kenji; Rigden, Daniel J.; Kim, Chu‐Young
• Is Part Of: Angewandte Chemie. Volume 126:Number 3(2014)
• Page Start: 843
• Page End: 847
• Publication Date: 2013-12-02
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201307404
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Echinomycin is a nonribosomal depsipeptide natural product with a range of interesting bioactivities that make it an important target for drug discovery and development. It contains a thioacetal bridge, a unique chemical motif derived from the disulfide bond of its precursor antibiotic triostin A by the action of an <italic>S</italic>‐adenosyl‐<sc>L</sc>‐methionine‐dependent methyltransferase, Ecm18. The crystal structure of Ecm18 in complex with its reaction products <italic>S</italic>‐adenosyl‐<sc>L</sc>‐homocysteine and echinomycin was determined at 1.50 Å resolution. Phasing was achieved using a new molecular replacement package called AMPLE, which automatically derives search models from structure predictions based on ab initio protein modelling. Structural analysis indicates that a combination of proximity effects, medium effects, and catalysis by strain drives the unique transformation of the disulfide bond into the thioacetal linkage.</p> </abstract>