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Biotechnology and molecular biology of the α-glucosidase inhibitor acarbose

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Abstract

The α-glucosidase inhibitor acarbose, O-{4,6-dideoxy-4[1s-(1,4,6/5)-4,5,6-trihydroxy-3-hydroxymethyl-2-cyclohexen-1-yl]-amino-α-d-glucopyranosyl}-(1→4)-O-α-d-glucopyranosyl-(1→4)-d-glucopyranose, is produced in large-scale fermentation by the use of strains derived from Actinoplanes sp. SE50. It has been used since 1990 in many countries in the therapy of diabetes type II, in order to enable patients to better control blood sugar contents while living with starch-containing diets. Thus, it is one of the latest successful products of bacterial secondary metabolism to be introduced into the pharmaceutical world market. Cultures of Actinoplanes sp. also produce various other acarbose-like components, of which component C is hard to separate during downstream processing, which is one of the most modern work-up processes developed to date. The physiology, genetics and enzymology of acarbose biosynthesis and metabolism in the producer have been studied to some extent, leading to the proposal of a new pathway and metabolic cycle, the “carbophore”. These data could give clues for further biotechnological developments, such as the suppression of side-products, enzymological or biocombinatorial production of new metabolites and the engineering of production rates via genetic regulation in future.

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Acknowledgements

We acknowledge excellent cooperation with the groups of A. Crueger and H. Wehlmann (Bayer AG), H. Pape (University of Muenster), H.G. Floss (University of Seattle) and H.J. Altenbach (BU Wuppertal) in this project. The work in the laboratories of the authors was supported by grants from Bayer AG (Leverkusen, Germany) and the German Ministry of Education and Research (BMBF grant BEO22-0310815).

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Wehmeier, U.F., Piepersberg, W. Biotechnology and molecular biology of the α-glucosidase inhibitor acarbose. Appl Microbiol Biotechnol 63, 613–625 (2004). https://doi.org/10.1007/s00253-003-1477-2

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