Acarbose, the first example of a carbophor?

• Applicants: Professor Dr. Erwin Schneider; Privatdozent Dr. Udo Wehmeier
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 12815386

The ¿¿glucosidase inhibitor acarbose, produced by strains of the genera Actinoplanes and Streptomyces, is a member of an unusual group of bacterial secondary metabolites, all of which inhibit various ¿¿glucosidases. Acarbose is used in the treatment of patients suffering from diabetes type II. Actinoplanes produces acarbose as part of a mixture of compounds called ¿acarbose homologs¿ which, depending on the carbon source, differ in the number of glucose residues at both, the reducing and the non-reducing end. Unlike its function as an inhibitor of ¿¿glucosidases, the benefits of acarbose for the producing organism are still not understood. According to a recent hypothesis acarbose and related compounds might function as so called ¿carbophors¿: Actinoplanes is thought to produce acarbose in order to prevent competitors in its natural habitat from utilizing starch as a carbon and energy source. This is achieved by its function as potent inhibitor of ¿¿glucosidases and of transport systems mediating the uptake of malto-oligosaccharides. Increasing amounts of free unbound acarbose can then be used as acceptor molecules for the uptake of glucose or oligosaccharides which are transferred to acarbose by the action of the acarviosyltransferase, AcbD and/or the ¿¿amylases AcbE/Z. The resulting longer homologs are transported into the cytoplasm where glucose units will then be released and shuttled into metabolism. Acarbose is phosphorylated and re-exported to start a new ¿carbophor cycle¿. The carbophor function has not yet been studied in detail and will be analysed in this application.

• DFG Programme: Research Grants