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Keywords
(5)
Crystal Structure
Directed Evolution
Enzyme
Site Directed Mutagenesis
Vitamin D
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Bioconversion of vitamin D to its active form by bacterial or mammalian cytochrome P450
Bioconversion of vitamin D to its active form by bacterial or mammalian cytochrome P450,10.1016/j.bbapap.2010.07.014,Biochimica Et Biophysica Acta-pro
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Bioconversion of vitamin D to its active form by bacterial or mammalian cytochrome P450
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Toshiyuki Sakaki
,
Hiroshi Sugimoto
,
Keiko Hayashi
,
Kaori Yasuda
,
Eiji Munetsuna
,
Masaki Kamakura
,
Shinichi Ikushiro
,
Yoshitsugu Shiro
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 D3 to 1α,25-dihydroxyvitamin D3. 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 1α,25-dihydroxyvitamin D3. 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 D3 to 1α,25-dihydroxyvitamin D3. 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.
Journal:
Biochimica Et Biophysica Acta-proteins and Proteomics - BBA-PROTEINS PROTEOMICS
, vol. 1814, no. 1, pp. 249-256, 2011
DOI:
10.1016/j.bbapap.2010.07.014
Cumulative
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