NOVEL 7beta-HYDROXYSTEROID DEHYDROGENASES AND THEIR USE

Abstract

The invention relates to novel 7β-hydroxysteroid dehydrogenases which are obtainable from bacteria of the genus Collinsella, especially of the strain Collinsella aerofaciens, to the sequences encoding said enzymes, to methods for producing said enzymes and to their use in the enzymatic conversion of cholic acid compounds, and especially in the production of ursodeoxycholic acid (UDCS). The invention also relates to novel methods for the synthesis UDCS.

Description

[0001]The invention relates to novel 7β-hydroxysteroid dehydrogenases obtainable from bacteria of the genus Collinsella, in particular of the strain Collinsella aerofaciens, the sequences coding for these enzymes, methods for the production of the enzymes and the use thereof in enzymatic conversions of cholic acid compounds, and in particular in the production of ursodesoxycholic acid (UDCA); also a subject of the invention are novel methods for the synthesis of UDCA.BACKGROUND OF THE INVENTION[0002]The active substances ursodesoxycholic acid (UDCA) and the corresponding diastereomer chenodesoxycholic acid (CDCA) have for many years been used for the medicinal treatment of gallstone problems. The two compounds differ only in the configuration of the hydroxy group on C atom 7 (UDCA: β configuration, COCA: α configuration). For the production of UDCA, various methods are described in the state of the art, which are carried out purely chemically or consist of a combination of chemical ...

AI Technical Summary

Benefits of technology

The patent describes a new method for producing UDCA using a specific enzyme found in bacteria. This enzyme converts cholic acid to UDCA through a simple chemical process, resulting in high conversion and selectivity without forming any byproducts. The use of recombinant enzymes makes the production of UDCA possible on a large scale.

Problems solved by technology

A serious disadvantage inter alia is as follows: since the chemical oxidation is not selective, the carboxy group and the 3α and 7α-hydroxy group must be protected by esterification.

Disadvantages in this method are that because of the equilibrium position of the catalyzed reaction a complete conversion is not possible, and that for the first step of the conversion two different enzymes must be used, which increases the process cost.

A disadvantage in the cofactor regeneration used there is that the coproduct formed can only be removed from the reaction mixture with great difficulty, so that the reaction equilibrium cannot be favorably influenced, which results in incomplete conversion of the educt.

However, a disadvantage in this method is the use of a 7β-HSDH from the pathogenic microorganism Clostridium absonum, and the need preparatively to purify the enzyme from the bacterial extract which additionally possesses undesired 7α-HSDH activity.

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