Modular microfluidic reactor and inline filtration system for the biocatalytic synthesis of chiral metabolites

Biocatalytic synthesis is now well established amongst catalytic methodologies as an extremely useful approach for the industrial synthesis of high-value compounds, due to its many advantages such as high reaction specificity and selectivity. However, engineering a biocatalytic process can be complex and time-consuming. This paper presents a modular microfluidic reactor and in-line filtration system for the rapid and small-scale evaluation of biocatalytic reactions. The system combines a substrate with a biocatalyst in free solution, incubates the two components until full conversion to product has been achieved, before extracting the product. The system has been applied to the transketolase-catalysed reaction of hydroxypyruvate (HPA) and glycolaldehyde (GA) to l-erythrulose, demonstrating complete conversion of substrate to product, complete retention of the enzyme and an overall yield of approximately 65%. The complete conversion of HPA and propanal to (3S)-1,3-dihydroxypentan-2-one with a mutant transketolase further demonstrated the applicability of the microfluidic system for organic synthesis.

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► We present integration of up- and downstream microfluidic bioprocess development.
► The system has been used for rapid small-scale evaluation of biocatalytic reactions.
► Complete conversion of substrate to product was achieved in the microreactor.
► The downstream filter unit allows the integration of any membrane type.
► Results from the microfluidic system are scalable.