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 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.

Evaluate the Levels of Serum Eotaxin-1, Myelin Basic Protein, and Some Immunological and Biochemical Markers in Iraqi Patients with Multiple Sclerosis

“…Calcitriol (1α, 25-dihydroxy vitamin D3) can be classified as a seco-steroid hormone. Vitamin D3 in humans is converted to calcitriol as an active final vitamin D3 metabolism product [17]. Research shows that the amount of vitamin D serum in MS patients influences the likelihood of getting MS and modulates disease activity.…”

Characterization of vitamin D3 biotransformation by the cell lysate of Actinomyces hyovaginalis CCASU-A11-2

“…A further experiment was accomplished to study the effect of pH, reaction temperature, and reaction time(Tang et al 2020 ) (Wang et al 2022 ), on vitamin D 3 bioconversion activity of the chromatographic active fraction. Our Findings revealed pH 7.8 was optimum for the biotransformation process.…”

Bioconversion of vitamin D3 into calcitriol by Actinomyces hyovaginalis isolate CCASU- A11-2

“…Several prior research studies have applied fermenters of various sizes to study the microbial conversion of vitamin D 3 into its hydroxylated derivatives (Kang et al 2006 , 2015a , b ; Abass et al 2011a , b ; Luo et al 2016 ; Tang et al 2020 ; Wang et al 2022 ). A previous study conducted by Sasaki et al 1991 , where 300 Streptomyces isolates were screened, found two strains with a conversion productivity of about 7.0 mg/L/min.…”

“…Accordingly, applied fermentation conditions (Run1) were established and these included: basal medium used for main culture and vitamin D 3 bioconversion; inoculum size of 2% v/v; agitation rate of 200 rpm; aeration rate of 1 vvm; initial pH of 7.8 (uncontrolled); temperature of 30 °C (before substrate addition) and of 28 °C (after substrate addition); addition of vitamin D 3 two days after the beginning of main culture and continual of the incubation process for additional four days. It is crucial to note that several of the conditions/factors previously described were based on a prior screening effort for optimizing vitamin D 3 bioconversion, by the research isolate, in a shake flask (Abass et al 2011b ; Wang et al 2022 ; ).…”