利用链霉菌菌株将25-羟基维生素D3和1α-羟基维生素D3转化为1α,25-二羟基维生素D3 。
Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.
作者信息
Sasaki J, Mikami A, Mizoue K, Omura S
机构信息
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
出版信息
Appl Environ Microbiol. 1991 Oct;57(10):2841-6. doi: 10.1128/aem.57.10.2841-2846.1991.
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.
为了酶促合成维生素D衍生物，我们筛选了约300株链霉菌属菌株。发现硬皮链霉菌FERM BP - 1370和粉红链霉菌FERM BP - 1574分别具有将25 - 羟基维生素D3和1α - 羟基维生素D3转化为1α,25 - 二羟基维生素D3的能力。FERM BP - 1370对25 - 羟基维生素D3的1α羟基化平均速率为6.9微克升-1分钟-1，FERM BP - 1574为7.0微克升-1分钟-1。特异性细胞色素P - 450抑制剂一氧化碳、SKF - 525 - A和甲吡酮抑制了FERM BP - 1370和FERM BP - 1574将1α - 和25 - 羟基维生素D3羟基化为1α,25 - 二羟基维生素D3的反应。通过全细胞悬浮液中的还原型CO差光谱检测了这些菌株的细胞色素P - 450。细胞色素P - 450的出现表明FERM BP - 1370和FERM BP - 1574的细胞色素P - 450可将25 - 和1α - 羟基维生素D3羟基化为1α,25 - 二羟基维生素D3。
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