Bioconversion for ursodeoxycholic acid using β-cyclodextrin included-chenodeoxycholic acid via immobilized cells of...

Ursodeoxycholic acid is a prevalent clinical drug widely used for hepatobiliary diseases. It offers the advantages of good efficacy, high sensitivity, low toxic side effects and multifunctionality. However, its poor water solubility and arduous biopreparation have always been obstacles. This work presents, for the first time, a continuous aerobic-biotransformation system for synthesizing ursodeoxycholic acid. The process utilizes immobilized Xanthomonas maltophilia cells with substrate chenodeoxycholic acid/β-cyclodextrin inclusion complexes. The designed inclusion complexes possessed favourable stability with solubility improved by 122 times comparing to the pure drug. Repeated batches transformation was carried out and reaction parameters like flow speed, fluid direction and filling volume were optimized. The results showed that X. maltophilia cells were successfully immobilized in the microspheres with typical shell-core structure and good abrasion resistance. The optimal reaction conditions were as follows: flow speed of 1.0 mL/min, fluid direction from bottom to top in a reverse orientation, and filling volume set to 1:1. The entire continuous reaction could be recycled in three consecutive batches with no decrease in the conversion of the products. This study provides a new strategy for the preparation of ursodeoxycholic acid via bioconversion, which is valuable to explore the aerobic-based strain for biotransformation.