Enzymatic synthesis of chiral amino-alcohols by coupling transketolase and transaminase-catalyzed reactions in a cascading continuous-flow microreactor system.
Enzymatic synthesis of chiral amino-alcohols by coupling transketolase and transaminase-catalyzed reactions in a cascading continuous-flow microreactor system.
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DOI：
10.1002/bit.26470
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发表时间：
2018-03
影响因子：
3.8
通讯作者：
Szita N
中科院分区：
文献类型：
--
作者：
Gruber P;Carvalho F;Marques MPC;O'Sullivan B;Subrizi F;Dobrijevic D;Ward J;Hailes HC;Fernandes P;Wohlgemuth R;Baganz F;Szita N
快速生物催化过程的开发和强化仍然是目前可用方法的挑战。手性氨基醇特别令人感兴趣，因为它们代表了生产复杂分子和光学纯药物的关键工业催化剂。(2S，3R）-2-氨基-1，3，4-丁三醇（ABT）是一种用于合成蛋白酶抑制剂和解毒剂的结构单元，可通过将转酮醇酶和转氨酶催化的反应偶联，从简单的非手性起始原料合成。然而，直到今天，还没有显示出完全转化，并且通常报告了长的反应时间，使得工艺修改和改进具有挑战性。在这篇文章中，我们提出了一种基于游离酶的新型微反应器方法，我们首次报道了ABT在间歇和连续流系统的耦合酶级联中的完全转化。使用由微反应器级联提供的反应的区室化，我们克服了抑制作用，增加了每单位体积的活性，并优化了各个反应条件。转酮醇酶催化的反应在10分钟内完成，体积活性为3.25 U ml−1。优化转氨酶催化反应后，体积活性达到10.8 U ml-1，这使得偶联反应在2小时内完全转化。所提出的方法说明了连续流微反应器如何应用于生物催化过程的设计和优化。
Rapid biocatalytic process development and intensification continues to be challenging with currently available methods. Chiral amino‐alcohols are of particular interest as they represent key industrial synthons for the production of complex molecules and optically pure pharmaceuticals. (2S,3R)‐2‐amino‐1,3,4‐butanetriol (ABT), a building block for the synthesis of protease inhibitors and detoxifying agents, can be synthesized from simple, non‐chiral starting materials, by coupling a transketolase‐ and a transaminase‐catalyzed reaction. However, until today, full conversion has not been shown and, typically, long reaction times are reported, making process modifications and improvement challenging. In this contribution, we present a novel microreactor‐based approach based on free enzymes, and we report for the first time full conversion of ABT in a coupled enzyme cascade for both batch and continuous‐flow systems. Using the compartmentalization of the reactions afforded by the microreactor cascade, we overcame inhibitory effects, increased the activity per unit volume, and optimized individual reaction conditions. The transketolase‐catalyzed reaction was completed in under 10 min with a volumetric activity of 3.25 U ml−1. Following optimization of the transaminase‐catalyzed reaction, a volumetric activity of 10.8 U ml−1 was attained which led to full conversion of the coupled reaction in 2 hr. The presented approach illustrates how continuous‐flow microreactors can be applied for the design and optimization of biocatalytic processes.
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影响因子：
5.2
作者：
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通讯作者：
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通讯作者：
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