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微生物用于甾体11α-羟化的中试研究

APPLICATION OF MICROORGANISMS FOR 11α-HYDROXYLATION OF STEROIDS ON A SCALE-UP EXPERIMENT

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【作者】 黄腾华李淳娟石美珍邱淑蕙彭贵章陈伯伦刘维达刘敏华

【Author】 Huang Tenghua;Li Chunjuan;Shi Maizhen;Qie Shuhui;Peng Guizhang;Chen Bolun;Liu Weida;Liu Minhua Shanghai Municipal Research Institute of Industrial Microbiology Shanghai 12th Pharmaceutical factory

【机构】 上海市工业微生物研究所上海市工业微生物研究所上海第十二制药厂

【摘要】 <正> 根霉80322的菌种筛选及发酵条件小试研究结果已有报道。本文叙述16-17α-环氧孕甾烯-4-3,20二酮以微生物进行 11α-羟化的中试结果。发现消除泡沫在发酵过程中是使转化正常进行的首要条件;消除泡沫后;发酵可在37±1℃中正常进行;孢子约8小时后长出菌丝;12小时起开始进行11α-羟化作用;发酵周期比5升三角瓶短;粗品收率91%以上;

【Abstract】 In a previous paper, we described the screening of Rhizopus 80322 and the re-sults of fermentation gained in a 5-liter conical flask. In this paper we describedthe results of experiments by the addition of steroids in the form of a micronizedpowder of 2% 16α, 17α-oxido-4-pregnene-3, 20-dione in 500-liter and 3000-liter fer-mentors. It was observed that foaming was the prime factor affecting the 11α-hydroxyla-tion during the fermentation. With the elimination of excessive foaming fermenta-tion was carried out normally at 37±1℃. Mycelia were grown out of germinatedspores 8 hours later, and 11α-hydroxylation started 12 hours after inoculation. Thefermentation period was shorter in this experiment than in that of 5-liter conicalflask. The yield of unpurified products was over 91%. While the yield of l1α-hydroxylation products for each run was 31%, that of the recycled substrates to bereoxygenated reached 30%. In each exprimentation, a volume of 80% of the totalfermentor capacity of steroid-spore suspension was used. Culturing methods for thescale-up of seed flask and optimal inoculation volume were also established.

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