Bioconversion of vitamin D3 to bioactive calcifediol and calcitriol as high-value compounds

Abstract Biological catalysis is an important approach for the production of high-value-added compounds, especially for products with complex structures. Limited by the complex steps of chemical synthesis and low yields, the bioconversion of vitamin D 3 (VD 3 ) to calcifediol and calcitriol, which are natural steroid products with high added value and significantly higher biological activity compared to VD 3 , is probably the most promising strategy for calcifediol and calcitriol production, and can be used as an alternative method for chemical synthesis. The conversion efficiency of VD 3 to calcifediol and calcitriol has continued to rise in the past few decades with the help of several different VD 3 hydroxylases, mostly cytochrome P450s (CYPs), and newly isolated strains. The production of calcifediol and calcitriol can be systematically increased in different ways. Specific CYPs and steroid C25 dehydrogenase (S25DH), as VD 3 hydroxylases, are capable of converting VD 3 to calcifediol and calcitriol. Some isolated actinomycetes have also been exploited for fermentative production of calcifediol and calcitriol, although the VD 3 hydroxylases of these strains have not been elucidated. With the rapid development of synthetic biology and enzyme engineering, quite a lot of advances in bioproduction of calcifediol and calcitriol has been achieved in recent years. Therefore, here we review the successful strategies of promoting VD 3 hydroxylation and provide some perspective on how to further improve the bioconversion of VD 3 to calcifediol and calcitriol.