Bioconversion of vitamin D(3) to bioactive calcifediol and calcitriol as high-value compounds

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.