Clean enzymatic production of ursodeoxycholic acid enabled by a newly identified NADH-dependent 7β-hydroxysteroid dehydrogenase

Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis

“…Furthermore, Yang et al reported the one-pot enzymatic cascade synthesis of ursodeoxycholic acid (72), which was isolated in 80% yield via enantioselective oxidation followed by reduction using 7α-hydroxysteroid dehydrogenase and 7β-hydroxysteroid dehydrogenase, respectively. 132 In this cascade synthesis, two cofactor regenerating enzymes, NADH oxidase (NOX) and FDH, were utilized effectively for the in situ regeneration of NAD + and NADH, respectively. Notably, in this cascade method, the by-products are water and carbon dioxide, which do not require any special treatment during downstream processing (Scheme 16).…”

Machine-Learning-Guided Engineering of an NADH-Dependent 7β-Hydroxysteroid Dehydrogenase for Economic Synthesis of Ursodeoxycholic Acid

“…Subsequently, several other NADH-dependent 7β-HSDHs have also been discovered by metagenomic mining techniques, but their use in the enzymatic synthesis of UDCA has not been investigated . Most recently, two novel NADH-dependent 7β-HSDHs were identified from Roseococcus sp . and Candidatus Ligilactobacillus excrementigallinarum, respectively, and both of them showed limited ability in production of UDCA.…”

“…23 Most recently, two novel NADH-dependent 7β-HSDHs were identified from Roseococcus sp. 31 and Candidatus Ligilactobacillus excrementigallinarum, 6 respectively, and both of them showed limited ability in production of UDCA.…”

Study on synthesis of ursodeoxycholic acid by reduction of 7-ketolithocholic acid in double aprotic solvents and molecular simulations

“…WP_213611802.1) and an NAD+-dependent 7α-HSDH (7α-hydroxysteroid dehydrogenase), with O2/NOX and HCOO−/FDH (formate dehydrogenase) systems for the regeneration of cofactors (NAD+ and NADH), 25 mM chenodeoxycholic acid was completely converted to UDCA in one-pot two-step cascade, with an 80% isolated yield. In this paper, the electrochemical method is used to prepare ursodeoxycholic acid, which is a relatively simple and safe process that does not require harsh reaction conditions and complex reaction steps (Yang et al 2023 ).

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