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NAD+ -Dependent Enzymatic Route for the Epimerization of Hydroxysteroids.

ABSTRACT: Epimerization of cholic and chenodeoxycholic acid (CA and CDCA, respectively) is a notable conversion for the production of ursodeoxycholic acid (UDCA). Two enantiocomplementary hydroxysteroid dehydrogenases (7?- and 7?-HSDHs) can carry out this transformation fully selectively by specific oxidation of the 7?-OH group of the substrate and subsequent reduction of the keto intermediate to the final product (7?-OH). With a view to developing robust and active biocatalysts, novel NADH-active 7?-HSDH species are necessary to enable a solely NAD+ -dependent redox-neutral cascade for UDCA production. A wild-type NADH-dependent 7?-HSDH from Lactobacillus spicheri (Ls7?-HSDH) was identified, recombinantly expressed, purified, and biochemically characterized. Using this novel NAD+ -dependent 7?-HSDH enzyme in combination with 7?-HSDH from Stenotrophomonas maltophilia permitted the biotransformations of CA and CDCA in the presence of catalytic amounts of NAD+ , resulting in high yields (>90?%) of UCA and UDCA.

SUBMITTER: Tonin F

PROVIDER: S-EPMC6681466 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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NAD+ -Dependent Enzymatic Route for the Epimerization of Hydroxysteroids.

Tonin Fabio F Otten Linda G LG Arends Isabel W C E IWCE

ChemSusChem 20181105 13

Epimerization of cholic and chenodeoxycholic acid (CA and CDCA, respectively) is a notable conversion for the production of ursodeoxycholic acid (UDCA). Two enantiocomplementary hydroxysteroid dehydrogenases (7α- and 7β-HSDHs) can carry out this transformation fully selectively by specific oxidation of the 7α-OH group of the substrate and subsequent reduction of the keto intermediate to the final product (7β-OH). With a view to developing robust and active biocatalysts, novel NADH-active 7β-HSDH ...[more]

PMID: 30265441

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