Optimising Continuous Flow Biocatalysis Processes for Fine Chemical Manufacturing

Lead Research Organisation: University of Leeds
Department Name: Chemical and Process Engineering

Abstract

Background: The integration of biocatalytic transformations into the synthesis of commercial fine chemical and pharmaceutical products is becoming increasingly widespread, with attendant enviromental and economic benefits (e.g. minimisation of chemical waste streams, avoiding expensive or scarce reagents/catalysts). Continuous flow biocatalysis has several advantages over batch alternatives. These advantages include avoiding the need for catalyst removal from the product stream, minimising equilibrium controlled limitations on yield and allosteric control. Current use of biocatalysis in continuous flow is, however, limited by several factors. These include the variable performance of the immobilization supports and the mismatching of these supports to the type of reactor (e.g. tubular vs continuous stirred-tank reactor), as well as issues in the separation of aqueous/organic streams. If these limitations can be overcome, not only will the biotransformation step be improved, but it also opens up possible telescoping with up/downstream chemo-catalytic steps, with positive impact upon the efficiency and sustainability of the process.
Aims and objectives: In this project, we will (a) optimise the performance of supported biocatalysts in different reactor configurations, (b) integrate continuous separation with the intention of facilitating downstream cascade reactions and/or co-factor recycling, (c) demonstrate the union of continuous bio- and chemo-catalysis processes for the synthesis of exemplar products (e.g. drug intermediates) on select targets chosen in collaboration with our industrial partners, and (d) understand the relationship between the catalyst and support to improve activity and longevity. We will exemplify the methods on two distinct enzyme classes to demonstrate the robustness and generality of the methods.
Applications and benefits: This work, which encompasses research in the EPSRC areas of Catalysis and Manufacturing Technologies (amongst others), will lead to greater uptake of sustainable technologies for the manufacture of fine chemicals (addressing the Manufacturing the Future theme) and medicines (Healthy Nation theme), thus delivering environmental and economic benefits to the UK.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022473/1 01/04/2019 30/09/2027
2271864 Studentship EP/S022473/1 01/10/2019 30/09/2023 Harrison Johnson-Evans