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Continuous steroid biotransformations in microchannel reactors

机译：微通道反应器中类固醇的连续生物转化

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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 byproduct. 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.
机译：随着过程的强化和生产平台的发展，在生物过程范围内使用基于微通道反应器的技术正在获得发展。这种趋势可归因于微通道反应器的一组特定特征，即与传统反应器相比，其质量和传热增强，并且易于处理且所需的体积较小。在目前的工作中，评估了通过胆固醇的酶促氧化生成4-胆甾烯-3-酮的连续生产过程，而没有形成任何副产物。生产是在水-有机两相系统的Y形微通道反应器中进行的。将底物从有机相输送至含有胆固醇氧化酶的水相，并且形成的产物分配回到有机相。然后迫使水相通过包含固定的过氧化氢酶的活塞流反应器。该步骤旨在减少在胆固醇氧化期间作为副产物形成的过氧化氢，以避免由于所述副产物而使胆固醇氧化酶失活。将该装置与传统反应堆和操作模式进行了比较。结果表明，微通道反应器的几何性能优于传统的搅拌釜和活塞流反应器，在减少的停留时间上达到了相似的转化率。将包含过氧化氢酶的活塞流反应器连接起来，可使水相重复使用，并保持30％的胆固醇氧化酶催化活性，同时消除了过氧化氢。在运行300小时后，最终产生了36 M的胆甾酮。

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