Abstract
Biocatalytic synthesis in continuous-flow microreactors is of increasing interest for the production of specialty chemicals. However, the yield of production achievable in these reactors can be limited by the adverse effects of high substrate concentration on the biocatalyst, including inhibition and denaturation. Fed-batch reactors have been developed in order to overcome this problem, but no continuous-flow solution exists. We present the design of a novel multi-input microfluidic reactor, capable of substrate feeding at multiple points, as a first step towards overcoming these problems in a continuous-flow setting. Using the transketolase-(TK) catalysed reaction of lithium hydroxypyruvate (HPA) and glycolaldehyde (GA) to l-erythrulose (ERY), we demonstrate the transposition of a fed-batch substrate feeding strategy to our microfluidic reactor. We obtained a 4.5-fold increase in output concentration and a 5-fold increase in throughput compared with a single input reactor.
Highlights
Microfluidic reactors are of increased interest for preparative synthetic work due to a variety of advantages such as improved heat and mass transfer, mixing, safety, process intensification, scalability and reproducibility
Since the scale-up to viable manufacturing processes requires work on the process design, reaction engineering and the optimisation of reaction conditions [28,29], the application of microreactor technology to transketolase-catalyzed carbon-carbon bond formation reactions is of fundamental interest [30]
We have described the cascading of a microfluidic reactor and a filtration system for biocatalytic asymmetric synthesis using transketolase [31]
Summary
Microfluidic reactors are of increased interest for preparative synthetic work due to a variety of advantages such as improved heat and mass transfer, mixing, safety, process intensification, scalability and reproducibility. Reactor systems allowing injection of substrates at multiple points have been demonstrated for the purpose of controlling exothermic chemical reactions These systems were designed for the continuous synthesis of allylcarbinol and of organometallic compounds, using multi-point feeding to control the formation of impurities and the generation of heat respectively [35,36,37]. Such systems have not been applied to the problem of substrate inhibition in biocatalytic reactions. We demonstrate the application of the reactor to the TK-catalysed reaction of lithium hydroxypyruvate (HPA) and glycolaldehyde (GA) to l-erythrulose (ERY; Scheme 1)
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