Figure 1.

A gene encoding 12β-HSDH completes the gut microbial epi-bile acid pathway. Cholic acid (CA) is converted to the oxo-intermediate, 7-oxodeoxycholic acid (7-oxoDCA), and further to ursoCA through the urso-bile acid pathway catalyzed by NAD(P)-dependent 7α- and 7β-HSDH. The secondary bile acid deoxycholic acid (DCA) is formed through the multi-step 7α-dehydroxylation of CA. DCA is biotransformed to 3-oxoDCA by 3α-HSDH and to isoDCA by 3β-HSDH in the iso-bile acid pathway. DCA can be converted to 12-oxolithocholic acid (12-oxoLCA) by 12α-HSDH and from 12-oxoLCA to epiDCA by 12β-HSDH. Examples of bacteria expressing each HSDH are shown below the reaction followed by corresponding gene annotations. Prior to this study, a gene encoding 12β-HSDH had not been identified