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Pathway Description
Biosynthesis of Ursodeoxycholic Acid (UDCA) and Lithocholic Acid (LCA) (bai operon)
Clostridium scindens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2025-04-08
Last Updated: 2025-07-31
The bai operon, responsible for bile acid metabolism, particularly the 7-α-dehydroxylation process, encodes a series of key enzymes involved in the transformation of primary bile acids like chenodeoxycholic acid (CDCA) into secondary bile acids such as lithocholic acid (LCA) and ultimately ursodeoxycholic acid (UDCA). This operon is activated by the presence of bile acids, which induce its expression, thereby facilitating the efficient utilization of these compounds by gut bacteria.The baiB gene encodes a bile acid-CoA ligase that activates bile acids by converting them into their CoA derivatives, a crucial step for subsequent enzymatic processing. Following this, baiF is responsible for encoding a bile acid-CoA hydrolase that removes the CoA group, yielding free bile acids necessary for further modifications. The gene baiC then encodes a 7-α-hydroxysteroid dehydratase, which catalyzes the conversion of bile acids at the C7 position, a key step in the 7-α-dehydroxylation pathway. Furthermore, baiE encodes a 7-α-dehydratase that facilitates the rate-limiting step of dehydroxylation, transforming intermediates into 3-oxo derivatives that will be later converted into LCA or UDCA.baiA additionally plays a role in converting 3-oxo bile acids back to their 7-dehydroxylated forms, aiding in the production of LCA. The subsequent enzymes, baiH and baiG, involve the complex series of transformations of the 3-oxo derivatives, ultimately leading to the biosynthesis of UDCA through a series of reductive steps facilitated by bai genes like baiN. In summary, the bai operon orchestrates a finely tuned series of enzymatic reactions that enable gut bacteria to efficiently metabolize endogenous bile acids, yielding bioactive secondary metabolites such as LCA and UDCA, which play significant roles in the modulation of lipid and glucose metabolism in the host
References
Biosynthesis of Ursodeoxycholic Acid (UDCA) and Lithocholic Acid (LCA) (bai operon) References
Wise, J.L. and Cummings, B.P., 2023. The 7-α-dehydroxylation pathway: An integral component of gut bacterial bile acid metabolism and potential therapeutic target. Frontiers in Microbiology, 13, p.1093420.
Vico-Oton, E., Volet, C., Jacquemin, N., Dong, Y., Hapfelmeier, S., Meibom, K.L. and Bernier-Latmani, R., 2024. Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid. BMC microbiology, 24(1), p.286.
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