Efficient synthesis of 7-oxo-lithocholic acid using a newly identified 7α-hydroxysteroid dehydrogenase

7-Oxo-lithocholic acid (7-oxo-LCA) is a key precursor for the enzymatic synthesis of the therapeutic bile acid ursodeoxycholic acid (UDCA). Chenodeoxycholic acid (CDCA) can be readily converted to 7-oxo-LCA by the 7α-hydroxysteroid dehydrogenase (7α-HSDH). However, the poor substrate tolerance of the current 7α-HSDH limits their practical applications. In this study, a new and natively NAD(+)-dependent Sm 7α-HSDH from Shewanella morhuae was identified, which exhibited a better substrate tolerance compared with other 7α-HSDHs. The purified Sm 7α-HSDH showed a high oxidative activity of 281 U mg −1 protein toward CDCA, with a catalytic efficiency ( k cat /K m ) of 7.47 × 10 3 mM −1 s −1 . In a preparative biotransformation (100 mL scale), 200 mM (∼80 g L −1 ) CDCA was almost completely oxidized to 7-oxo-LCA in 1 h, with a 78% isolated yield and a space-time yield (STY) of up to 1418 g L −1 d −1 , which is so far the highest productivity for biosynthesis of 7-oxo-LCA from CDCA. These results demonstrate the great potential of Sm 7α-HSDH as a promising biocatalyst for UDCA synthesis.