Bioconversion of vitamin D₃ 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 D₃ (VD₃) to calcifediol and calcitriol, which are natural steroid products with high added value and significantly higher biological activity compared to VD₃, 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 VD₃ to calcifediol and calcitriol has continued to rise in the past few decades with the help of several different VD₃ 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 VD₃ hydroxylases, are capable of converting VD₃ to calcifediol and calcitriol. Some isolated actinomycetes have also been exploited for fermentative production of calcifediol and calcitriol, although the VD₃ 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 VD₃ hydroxylation and provide some perspective on how to further improve the bioconversion of VD₃ to calcifediol and calcitriol.