Bioconversion of vitamin D to its active form by bacterial or mammalian cytochromes P450.

Biochim Biophys Acta. 2010 Jul 20. Epub ahead of print
Sakaki T, Sugimoto H, Hayashi K, Yasuda K, Munetsuna E, Kamakura M, Ikushiro S, Shiro Y.
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.

Bioconversion processes, including specific hydroxylations, promise to be useful for practical applications because chemical syntheses often involve complex procedures. One of the successful applications of P450 reactions is the bioconversion of vitamin D(3) to 1alpha,25-dihydroxyvitamin D(3). Recently, a cytochrome P450 gene encoding a vitamin D hydroxylase from the CYP107 family was cloned from Pseudonocardia autotrophica and is now applied in the bioconversion process that produces 1alpha,25-dihydroxyvitamin D(3). In addition, the directed evolution study of CYP107 has significantly enhanced its activity. On the other hand, we found that Streptomyces griseolus CYP105A1 can convert vitamin D(3) to 1alpha,25-dihydroxyvitamin D(3). Site-directed mutagenesis of CYP105A1 based on its crystal structure dramatically enhanced its activity. To date, multiple vitamin D hydroxylases have been found in bacteria, fungi, and mammals, suggesting that vitamin D is a popular substrate of the enzymes belonging to the P450 superfamily. A combination of these cytochrome P450s would produce a large number of compounds from vitamin D and its analogs. Therefore, we believe that the bioconversion of vitamin D and its analogs is one of the most promising P450 reactions in terms of practical application. Copyright © 2010. Published by Elsevier B.V. PMID: 20654743