Optimization strategy and application of ursodeoxycholic acid biosynthesis
Ursodeoxycholic acid(UDCA)is an endogenous bile acid,which is a therapeutic and anticancer drug for a va-riety of liver diseases.The chemical synthesis of UDCA have many problems,such as complex reaction process,environ-mentally unfriendly,low yield and so on.But the green,efficient and safe biosynthesis has become the focus of research and industrial production.UDCA biosynthesis is based on cheap chenodeoxycholic acid(CDCA),cholic acid(CA)or lithocholic acid(LCA)as substrates,through free enzyme catalysis or whole cell synthesis,in which CDCA is the most widely used substrate.Free enzyme catalyzed one pot,one-step/two-step method using hydroxysteroid dehydrogenase(HSDHs);Whole cell synthesis is using engineering strains expressing hsdhs or P450 monooxygenase with C-7 hydroxyl-ation activity.Although the yield of UDCA biosynthesis is high,it still has some limitations in industrial production,inclu-ding enzyme activity,stability,expression conditions and catalytic system of key enzymes,and microbial pathogenicity.Therefore,it is very important to optimize the synthesis strategy of ursodeoxycholic acid.In this review,the strategies for optimizing ursodeoxycholic acid biosynthesis in recent years,such as the modification of key enzymes by protein engineer-ing technology,the mining and modification of cofactor specific hsdhs,cofactor regeneration,immobilized enzyme technol-ogy and engineering strains,were reviewed.The advantages and disadvantages of different strategies were analyzed,and the development direction of industrialization of ursodeoxycholic acid biosynthesis was prospected.
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