Microbial biotransformation of vitamin D3 into biologically active calcitriol

Summary

Deficiency of formation of vitamin D3 active forms in human body, especially calcitriol, may be due to genetic or physiological factors including hepatic and renal disorders. This causes several diseases such as rickets, osteoporosis, hyperparathyroidism and psoriasis. Synthetic calcitriol has been used clinically to treat such disease states but unfortunately, its chemical synthesis, especially regio- and stereo- selective introduction of a hydroxyl group at C-1, is a very expensive and complicated procedure. Such criteria have necessitated the need to apply enzymatic chemistry using microorganisms to hydroxylate vitamin D3 at the 1α- and/or 25-positions. Microorganisms that are capable of hydroxylating vitamin D3 compounds are actually very limited and found to be belonging to the order Actinomycetales particularly the two genera Streptomyces and Amycolata. So, there is a strong need for the discovery of new microbial isolates capable of biotransfroming vitamin D3 into calcitriol. Moreover, on the Egyptian scale, there has been no attempt to biotransfrom vitamin D3 into calcitriol using microorganisms and no bacterial strains, capable of biotransforming vitamin D3 into calcitriol, have been isolated from Egyptian soils. A previous research was conducted in our laboratory to study biotransformation of vitamin D3 into calcitriol using local bacterial isolates collected from different soil samples in Egypt. We accomplished the biotransformation of vitamin D3 into calcitriol with Actinomyces hyovaginalis species. Based upon the previous findings, this proposal aims to optimize the biotransformation ability of the study isolate using different techniques including physiological optimization of biotransformation culture medium and conditions and genetic manipulation using induced mutation and protoplast fusion.  Application of the isolate cell lysate in the biotransformation process instead of the intact bacterial cells and enzyme immobilization will be studied for improvement and making the biotransformation process cost effective. The results obtained would help for calcitriol production from vitamin D3 for industrial applications. The significance of this proposal is based on continuing the global work of different researchers and nationwide implementing production calcitriol from biologically inert vitamin D3 by biological means, which provides a much more cheaper and easier alternative to chemical synthesis

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