Sequence and structure-guided discovery of a novel NADH-dependent 7β-hydroxysteroid dehydrogenase for efficient biosynthesis of ursodeoxycholic acid

The Impact of Bilirubin on 7α- and 7β- Hydroxysteroid Dehydrogenases: Spectra and Docking Analysis

“…So this region is the most probably binding area of bilirubin and 7α-HSDH. From Figure S1, we can see the most probably binding site of bilirubin was close to NADP + , and bilirubin may be bound with Arg (16), Arg (20), Arg (194) and Glu (221) of 7α-HSDH. The previous study had demonstrated that bilirubin was also most possibly binding with arginine residue of human serum albumin [43].…”

“…Relying on the circulation of nicotinamide adenine dinucleotide phosphate (NADP + and NADPH), the two steps coupling-reaction is highly efficient in preparation of UDCA and TUDCA. 7α-and 7β-HSDH belong to short chain dehydrogenase/reductase (SDR) family, which have been discovered from series of gut microbes, such as Clostridium absonum [17], Bacteroides fragilis [18], and Xanthomonas maltophilia [19], Candidatus Ligilactobacillus [20]. Besides, there are some progresses of 7α-and 7β-HSDH in application.…”

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

“…Ursodeoxycholic acid (UDCA), a pharmaceutically active natural product discovered in the bile of the black bears (Ursus thibetanus), is capable of solubilizing cholesterol gallstones and improving the liver function in cholestatic diseases. − In 1997, UDCA became the first drug approved by the US Food and Drug Administration (FDA) for the treatment of primary biliary cirrhosis . The main natural source of UDCA is the bear bile, which is a traditional Chinese health food and medicine obtained by biliary catheterization of farmed bears .…”

“…1−5 In 1997, UDCA became the first drug approved by the US Food and Drug Administration (FDA) for the treatment of primary biliary cirrhosis. 6 The main natural source of UDCA is the bear bile, which is a traditional Chinese health food and medicine obtained by biliary catheterization of farmed bears. 5 Since black bears have become a kind of scarce bioresource and are on the verge of extinction, the extraction of UDCA from the bile of live bears is not only unsustainable but also contrary to humanitarianism.…”

“…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.…”