Dual Flow Reactor Approach for the Chemoenzymatic Production of Chenodeoxycholic Acid, a Precursor to Ursodeoxycholic Acid

Chenodeoxycholic acid, a precursor to ursodeoxycholic acid, can be synthesized from inexpensive cholic acid through a two-step chemoenzymatic route. Here, a dual flow reactor system was developed to intensify this process. First, a packed-bed reactor with coimmobilized enzymes achieved complete conversion of 50 mM cholic acid to 12-oxochenodeoxycholic acid, achieving a space-time yield of 5831 g·L⁻¹·d⁻¹, significantly surpassing the batch mode (1632 g·L⁻¹·d⁻¹). Subsequently, a PTFE flow reactor facilitated the Wolff-Kishner-Huang reduction, producing chenodeoxycholic acid with a space-time yield of 3629 g·L⁻¹·d⁻¹, outperforming the batch mode (1555 g·L⁻¹·d⁻¹). This work highlights a safe and efficient platform for chemoenzymatic chenodeoxycholic acid synthesis and provides a generalizable strategy for industrial bile acid production.