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

Toshiyuki Sakaki, Hiroshi Sugimoto, Keiko Hayashi, Kaori Yasuda, Eiji Munetsuna, Masaki Kamakura, Shinichi Ikushiro, Yoshitsugu Shiro

Research output: Contribution to journalReview article

25 Citations (Scopus)

Abstract

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 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 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.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1814
Issue number1
DOIs
Publication statusPublished - 01-01-2011

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Bioconversion
Vitamin D
Cytochrome P-450 Enzyme System
Calcitriol
Cholecalciferol
Mixed Function Oxygenases
Hydroxylation
Mutagenesis
Gene encoding
Mammals
Streptomyces
Cytochromes
Site-Directed Mutagenesis
Fungi
Bacteria
Crystal structure
Substrates
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

Cite this

Sakaki, Toshiyuki ; Sugimoto, Hiroshi ; Hayashi, Keiko ; Yasuda, Kaori ; Munetsuna, Eiji ; Kamakura, Masaki ; Ikushiro, Shinichi ; Shiro, Yoshitsugu. / Bioconversion of vitamin D to its active form by bacterial or mammalian cytochrome P450. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2011 ; Vol. 1814, No. 1. pp. 249-256.
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Bioconversion of vitamin D to its active form by bacterial or mammalian cytochrome P450. / Sakaki, Toshiyuki; Sugimoto, Hiroshi; Hayashi, Keiko; Yasuda, Kaori; Munetsuna, Eiji; Kamakura, Masaki; Ikushiro, Shinichi; Shiro, Yoshitsugu.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1814, No. 1, 01.01.2011, p. 249-256.

Research output: Contribution to journalReview article

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AU - Munetsuna, Eiji

AU - Kamakura, Masaki

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