TRANSFORMATION OF 25-HYDROXYVITAMIN-D3 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 scelerotialus FERM BP-1370 and Streptomyces roseosporus 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-mu-g liter-1 min-1 with FERM BP-1370 and 7.0-mu-g 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.