Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.
To enzymatically synthesize vitamin D derivatives, we screened about 300 Streptomyces sp. strains. Streptomyces sclerotialus FERM BP-1370 and Streptomyces roseoporus FERM BP-1574 were found to have the ability to convert 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, respectively, to 1 alpha, 25-dihydroxyvitamin D3. The average rates of 1 alpha hydroxylation of 25-hydroxyvitamin D3 were 6.9 micrograms liter-1 min-1 with FERM BP-1370 and 7.0 micrograms liter-1 min-1 with FERM BP-1574. The specific cytochrome P-450 inhibitors carbon monoxide, SKF-525-A, and metyrapone inhibited the hydroxylation of 1 alpha- and 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by FERM BP-1370 and FERM BP-1574. The cytochromes P-450 of these strains were detected by reduced CO difference spectra in the whole-cell suspensions. The appearance of cytochrome P-450 suggests that the cytochromes P-450 of FERM BP-1370 and FERM BP-1574 carry out the hydroxylation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3.
Sasaki
J
J
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Mikami
A
A
Mizoue
K
K
Omura
S
S
D001711:Biotransformation; D002112:Calcifediol / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004347:Drug Interactions; D006887:Hydroxycholecalciferols / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006900:Hydroxylation / Q000187:drug effects; D013302:Streptomyces / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism*
D006887:Hydroxycholecalciferols; D003577:Cytochrome P-450 Enzyme System; D002117:Calcitriol; D002112:Calcifediol; C008088:alfacalcidol