title: Enzymatic routes for the synthesis of ursodeoxycholic acid.
abstract: Ursodeoxycholic acid, a secondary bile acid, is used as a drug for the treatment of various liver diseases, the optimal dose comprises the range of 8-10mg/kg/day. For industrial syntheses, the structural complexity of this bile acid requires the use of an appropriate starting material as well as the application of regio- and enantio-selective enzymes for its derivatization. Most strategies for the synthesis start from cholic acid or chenodeoxycholic acid. The latter requires the conversion of the hydroxyl group at C-7 from α- into β-position in order to obtain ursodeoxycholic acid. Cholic acid on the other hand does not only require the same epimerization reaction at C-7 but the removal of the hydroxyl group at C-12 as well. There are several bacterial regio- and enantio-selective hydroxysteroid dehydrogenases (HSDHs) to carry out the desired reactions, for example 7α-HSDHs from strains of Clostridium, Bacteroides or Xanthomonas, 7β-HSDHs from Clostridium, Collinsella, or Ruminococcus, or 12α-HSDH from Clostridium or from Eggerthella. However, all these bioconversion reactions need additional steps for the regeneration of the coenzymes. Selected multi-step reaction systems for the synthesis of ursodeoxycholic acid are presented in this review.
authors.affiliation: evocatal GmbH, Alfred-Nobel-Str. 10, 40789 Monheim am Rhein, Germany. Electronic address: t.eggert@evocatal.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Eggert
authors.affiliation: Institute of Molecular Enzyme Technology, Heinrich-Heine-University of Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bakonyi
authors.affiliation: Institute of Molecular Enzyme Technology, Heinrich-Heine-University of Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich, Germany. Electronic address: w.hummel@fz-juelich.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Hummel
mesh_terms: D039903:Actinobacteria / Q000201:enzymology; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000737:chemistry; D019826:Cholic Acid / Q000737:chemistry; D003013:Clostridium / Q000201:enzymology; D004926:Escherichia coli; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000737:chemistry; D014580:Ursodeoxycholic Acid / Q000096:biosynthesis* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; D006913:Hydroxysteroid Dehydrogenases; C031932:7 beta-hydroxysteroid dehydrogenase; C025376:7 alpha-hydroxysteroid dehydrogenase; D019826:Cholic Acid
keywords: Bile acids; Chenodeoxycholic acid; Cholic acid; Hydroxysteroid dehydrogenases; Ursodeoxycholic acid