Biocatalytic production of cholic acid derivatives with hydroxysteroid dehydrogenases

Michael Braun, doctoral thesis Technische Universität München, 2011

Ursodeoxycholic acid, which is used as pharmaceutical for the treatment of gallstones, is presently synthesized with a complex chemical process from cholic acid. Hydroxysteroid dehydrogenases catalyze the oxidation as well as the reduction of bile salts and offer alternative biocatalytic routes in the synthesis of ursodeoxycholic acid. Various enzyme systems for cell-free and whole-cell approaches were optimized concerning reaction rate and inhibitions. Alternative biocatalytic processes with integrated cofactor regeneration were developed based on kinetic modeling and simulation studies. Especially the application of whole cells enabled the almost complete conversion of high concentrations of cholic acid. Thus the current seven-step chemical synthesis can be reduced to four (oxidative route) or three (reductive route) chemical-enzymatic steps, respectively.


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