Review of Progress in Enzymatic Production of Ursodeoxycholic Acid
Ursodeoxycholic acid(UDCA)is the clinically preferred drug for treating various hepatobiliary diseases and plays an adjuvant role in some cancers and other diseases.However,the environmental concerns,harsh reaction conditions,low yield,and labor-intensive approaches associated with the chemical synthesis of UDCA often severely restrict its industrial production and utilization.Consequently,the primary area of study for UDCA synthesis has gradually shifted to green biosynthesis technology,which offers the benefits of a quick synthetic pathway,high yield,benign reaction conditions,and low cost.Currently,individuals utilize affordable and easily accessible lithocholic acid(LCA),chenodeoxycholic acid(CDCA),or cholic acid(CA)as substrates for enzymatic synthesis of UDCA or whole-cell transformation synthesis.Since the primary function of enzymes in biosynthesis is to convert substrates to UDCA,the development and design of 7α/β-hydroxysteroid dehydrogenase(7α/β-HSDH)and P450 monooxygenase with specific coenzyme dependence,high enzyme activity,high stability,and high substrate concentration tolerance have emerged as research hotspots.Biosynthesis relies mainly on biological enzymes'specificity to convert substrates into UDCA.Thus,hydroxysteroid dehydrogenase(7α/β-HSDH)and P450 monooxygenase with specific coenzyme dependence,high enzymatic activity,high stability,and high substrate tolerance need to be designed and developed.This study reviews the green synthesis technique of UDCA,discusses the benefits and drawbacks of the current biosynthesis,and looks ahead to future development directions to achieve sustainable,safe,effective,and green biomanufacturing of UDCA.
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维普
