Novel whole-cell biocatalysts with recombinant hydroxysteroid dehydrogenases for the asymmetric reduction of dehydrocholic acid

Applied Microbiology and Biotechnology
Michael BraunDirk Weuster-Botz

Abstract

Ursodeoxycholic acid is an important pharmaceutical so far chemically synthesized from cholic acid. Various biocatalytic alternatives have already been discussed with hydroxysteroid dehydrogenases (HSDH) playing a crucial role. Several whole-cell biocatalysts based on a 7α-HSDH-knockout strain of Escherichia coli overexpressing a recently identified 7β-HSDH from Collinsella aerofaciens and a NAD(P)-bispecific formate dehydrogenase mutant from Mycobacterium vaccae for internal cofactor regeneration were designed and characterized. A strong pH dependence of the whole-cell bioreduction of dehydrocholic acid to 3,12-diketo-ursodeoxycholic acid was observed with the selected recombinant E. coli strain. In the optimal, slightly acidic pH range dehydrocholic acid is partly undissolved and forms a suspension in the aqueous solution. The batch process was optimized making use of a second-order polynomial to estimate conversion as function of initial pH, initial dehydrocholic acid concentration, and initial formate concentration. Complete conversion of 72 mM dehydrocholic acid was thus made possible at pH 6.4 in a whole-cell batch process within a process time of 1 h without cofactor addition. Finally, a NADH-dependent 3α-HSDH from Comam...Continue Reading

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Dec 31, 2010·Biotechnology and Bioengineering·Michael BraunDirk Weuster-Botz

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Citations

Aug 19, 2014·Journal of Biotechnology·Thorsten EggertWerner Hummel
Mar 24, 2017·Journal of Industrial Microbiology & Biotechnology·Jie ShiZhengtao Wang
Mar 10, 2018·Beilstein Journal of Organic Chemistry·Fabio Tonin, Isabel W C E Arends
Aug 28, 2021·Microorganisms·Franziska Maria FellerBodo Philipp

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