The biosynthesis of ursocholic acid, a secondary bile acid, is closely associated with the enzymatic activities encoded by the hdh operon in Clostridium absonum. This operon includes two contiguous genes: hdhA, encoding the 7α-hydroxysteroid dehydrogenase (7α-HSDH), and hdhB, coding for the 7β-hydroxysteroid dehydrogenase (7β-HSDH). The process begins with the enzyme 7α-HSDH, which catalyzes the oxidation of cholic acid (CA) at the 7α-hydroxy position, converting it into a 7-keto intermediate. Subsequently, the 7β-HSDH reduces this keto intermediate, but in a stereoselective manner that introduces a 7β-hydroxy group, resulting in the formation of ursocholic acid. The operon appears to be co-regulated, facilitating a coordinated response to bile acids, with promoter and regulatory sequences identified upstream of hdhA and hdhB. The biosynthetic pathway mediated by this operon exemplifies a stereospecific transformation that alters the aromatic configuration of bile acids, enabling bacteria like C. absonum to produce functionally diverse secondary bile acids such as ursocholic acid, which play pivotal roles in host-microbiome interactions and possess potential therapeutic properties.

ursodeoxycholic acid secondary bile acid biosynthesis (hdh operon) References