Continuous steroid biotransformations in microchannel reactors
Continuous steroid biotransformations in microchannel reactors
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DOI：
10.1016/j.nbt.2011.10.001
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发表时间：
2012-01-15
影响因子：
5.4
通讯作者：
Plazl, Igor
中科院分区：
文献类型：
--
作者：
Marques, Marco P. C.;Fernandes, Pedro;Plazl, Igor
在生物工艺范围内使用基于微通道反应器的技术作为工艺强化和生产平台的势头正在增强。这种趋势可归因于微通道反应器的一组特殊特征，即与传统反应器相比，质量和热量传递增强，操作更容易，所需体积更小。在本工作中，评估了通过酶氧化胆固醇而不形成任何副产物的连续生产4-胆固醇-3- 1的过程。在水-有机两相体系中，在y型微通道反应器中进行生产。底物从有机相传递到含胆固醇氧化酶的水相，产物形成分区返回有机相。然后将水相强行通过塞流反应器，其中含有固定化过氧化氢酶。这一步骤旨在减少胆固醇氧化过程中作为副产物形成的过氧化氢，以避免因副产物而导致胆固醇氧化酶失活。该装置与传统反应器和操作模式进行了比较。结果表明，微通道反应器的几何形状优于传统的搅拌槽和塞流反应器，在减少停留时间的情况下达到相似的转化率。将含有过氧化氢酶的塞流反应器偶联在一起，使水相复用，在去除过氧化氢的同时，胆固醇氧化酶的催化活性保持在30%。经过300小时的运行，最终生产了36 M的胆甾酮。
The use of microchannel reactor based technologies within the scope of bioprocesses as process intensification and production platforms is gaining momentum. Such trend can be ascribed a particular set of characteristics of microchannel reactors, namely the enhanced mass and heat transfer, combined with easier handling and smaller volumes required, as compared to traditional reactors. In the present work, a continuous production process of 4-cholesten-3-one by the enzymatic oxidation of cholesterol without the formation of any by-product was assessed. The production was carried out within Y-shaped microchannel reactors in an aqueous-organic two-phase system. Substrate was delivered from the organic phase to aqueous phase containing cholesterol oxidase and the product formed partitions back to the organic phase. The aqueous phase was then forced through a plug-flow reactor, containing immobilized catalase. This step aimed at the reduction of hydrogen peroxide formed as a by-product during cholesterol oxidation, to avoid cholesterol oxidase deactivation due to said by-product. This setup was compared with traditional reactors and modes of operation. The results showed that microchannel reactor geometry outperformed traditional stirred tank and plug-flow reactors reaching similar conversion yields at reduced residence time. Coupling the plug-flow reactor containing catalase enabled aqueous phase reuse with maintenance of 30% catalytic activity of cholesterol oxidase while eliminating hydrogen peroxide. A final production of 36 M of cholestenone was reached after 300 hours of operation.