Continuous-Flow Biochemical Reactors: Biocatalysis, Bioconversion, and Bioanalytical Applications Utilizing Immobilized Microfluidic Enzyme Reactors

Abstract

The utilization of continuous-flow biochemical reactors, including biocatalysis, biotransformation, and biochemical interaction based flow-analytical systems, and enzyme reactors are recently the focus of attention to produce fine biochemicals and also show great potential in bioanalytical applications. Continuous-flow biochemical processes implemented in microstructured reactors enable short development time to production scale utilizing enzymatic processes to efficiently fulfill the current needs of the fine biochemical and pharmaceutical industry. Immobilization of the enzymes is preferable because it usually enhances their stability, and in some instances, immobilized enzymes can even be reused multiple times. In this review on the continuous-flow biochemical reactors, first the enzyme immobilization strategies will be briefly discussed followed by summarizing the recent developments in the field of immobilized enzyme microflow reactors for biocatalysis, bioconversion and bioanalytical purposes.

Flow-based stereoselective reduction of ketones using an immobilized ketoreductase/glucose dehydrogenase mixed bed system

“…Flow-based biocatalysis has recently attracted interest for screening, optimizing or setting up preparative biotransformations [6,7]. Biotransformations such as hydrolysis and formation of esters [8][9][10][11][12], formation of C-C bonds using transketolases [13], preparation of monosaccharides [14] and oligosaccharides [15], synthesis of nucleosides [16], interconversion of carbonyls and amines using transaminases [17,18], and peptide condensation [19] have been reported in the last few years.…”

Sucrose Hydrolysis in a Bespoke Capillary Wall-Coated Microreactor

“…Microreactors have already become a key component in chemical synthesis, yet its potential in biocatalysis, with the exception to the microwell format in process development, has not been fully capitalized, although their application in some relevant reaction systems supports the validity of the approach [11]. This is partly related to the ability of biocatalysts to operate under mild conditions where the generation of toxic and/or explosive compounds does not occur and therefore safety issues are usually not relevant.…”

Magnetic Microreactors with Immobilized Enzymes—From Assemblage to Contemporary Applications

“…A diversity of enzyme immobilization procedures for continuous-flow operation systems have been reported, differing in specificity, efficiency, simplicity, and purpose [30]. There are approaches that require genetic manipulation, like the use of genetically encoded tags, which results in an exact site-specific immobilization.…”