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Adrenal corticosteroids, as an important part of the steroid hormone drugs, a class of drugs is indispensable clinical. Commonly used natural steroidal compounds as raw materials, the use of synthetic chemical and microbial transformation combined process, including microbiological method for conversion of C 11 - the hydroxylation and C. 1 2 - dehydrogenation reaction is a key step in the synthesis process. C 11 bit of hydroxyl groups on the introduction of the anti-inflammatory activity of the adrenal cortex hormones drugs is essential, while the C 1,2 the location import double bond, can be multiplied increase its anti-inflammatory effects. In this paper, Epoxyprogesterone as raw material, Rhizopus nigricans 11α-hydroxylation reaction, the short spines Cunninghamella mold 11β-hydroxylation, simple Arthrobacter C 1,2 - dehydrogenation process carried optimized study steroid drugs biocatalysis process. 11α-hydroxylation process Rhizopus nigricans first to determine the optimal pH, optimizing the carbon source, and the establishment of the addition of sodium dodecyl benzene sulfonate aqueous suspension feeding mode in 3.7L fermenter amplification experiments, feeding concentrations up to 15g / L, the conversion rate of up to 49.2%, the and stable catalytic process. Confirmed the second the short spines Cunninghamella mold having a capacity of the 11β-hydroxylation, but the reaction byproducts more catalytic process instability. Its conversion process in the operating parameters, such as pH, speed, inoculum size, medium, etc. is optimized, the 10L fermenter enlarged experiment, feed concentration of 2g / L, 11β-hydroxylation product yield can be stably at 35%. The dehydrogenation process simple Arthrobacter the new technology research. Tween-80 emulsion feeding, and the response surface method optimization; build a water / n-hexane two-phase reaction system; study NaCS / PDMDAAC microcapsules immobilized Arthrobacter simplex cell culture; to use immobilization simple Arthrobacter in airlift reactor with water / n-hexane two-phase reaction system for the dehydrogenation process, combined with Tween-80 emulsified feed optimal additive reaction 2h which can achieve a high conversion rate of 97.54%, 5 batch repeat feeding semi-continuous production batch conversion rate of 95% or more. Last try stable catalytic performance Rhizopus nigricans and simple Arthrobacter mixed fermentation culture using resting cell transformation process to achieve step by hydroxylation and dehydrogenation reaction of epoxy progesterone, to establish the optimum process conditions phosphate buffer solution pH 6.0, the optimum feed concentration of 2g / L, multiple batches of the results of the repeated experiments showed that the fermentation of the mixing system has a certain stability.
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