Isolation of Fidaxomicin and Shunt Metabolites from Actinoplanes deccanensis

Abstract

A protocol for the isolation of the antibiotic fidaxomicin (Fdx) from Actinoplanes deccanensis and the isolation of shunt metabolites from A. deccanensis fdxG2− is reported. We constructed the mutant strain A. deccanensis fdxG2− by genetic manipulation which enabled the isolation of shunt metabolites as useful starting points for semisynthetic analogues of Fdx. Furthermore, a synthetic protocol for the conversion of complex A. deccanensis fdxG2− extracts into the single compound FdxG2-OH via methanolysis is presented. This synthetic procedure is complemented by images and practical notes. Full structure assignment is given in the SI and the characterization data files are published to aid experimentalists. The protocol is also suitable as an undergraduate laboratory project. We hope to facilitate research into new Fdx derivatives through the availability of this procedure.