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Enzymatic cascade biotransformations in digitally manufactured continuous-flow bioreactors

Project description

Lowering the cost of biocatalyst production with 3D printing

Biocatalysts can enable the production of more complex medicines, but they are currently expensive and time-consuming. With funding from Marie Skłodowska-Curie Actions, the FlowBioCat project will overcome current limitations on the chemical engineering of biocatalysts by developing 3D-printed reactors that optimise mixing at low flow rates. Instead of being immobilised in packed-bed reactors, the project will utilise tailored surface modification techniques with ionic liquids. This change will allow for stable biocatalyst preparations with more active sites, increasing productivity. This breakthrough in biochemical engineering has the potential to lower the cost and waste of drug production while simultaneously boosting supply and efficiency.

Objective

Within Industrial Biotechnology, applied biocatalysis is poised to transform drug discovery and development by pharmaceutical industry. Enzymes as catalysts, allow for synthetic chemists to generate molecular complexity avoiding costly and time-consuming protection and deprotection steps. However, the high cost associated to their use, especially if a co-factor is required, the low substrate tolerance and productivity and the difficulties for scale-up, strongly limit the industrial uptake of these processes. The combination of enzyme immobilisation and continuous flow (CF), offers an opportunity to overcome these limitations. Enzymatic performance and recyclability can be dramatically improved by immobilisation and generic problems such as low productivity and substrate inhibition effect can be solved using CF. During the last years, enzymes have been most commonly immobilised in packed bed reactors. However, the very low flow rates required to achieve full conversion, decrease the mixing and make the system look closer to a batch reaction (with its generic problems). Here we aim to address these limitations through the design and manufacture of 3D Printed (3DP) reactors that combine optimised mixing at low flow rates, with tailored surface modification techniques with ionic liquids (ILs) for stable biocatalyst preparation and higher number of active sites. 3DP facilitates the generation of complex geometries in a variety of materials based on ILs, tailored to optimise enzyme stability. The aim of this proposal is to integrate chemical engineering (3DP continuous flow reactors) and biocatalysis (stable and recyclable immobilised enzymes) to develop more efficient biotransformations in flow, easy and effective immobilisation of enzymes and significantly promote sustainable development of IB. It will have a direct impact in the EU from an environmental, economic and social perspective, lowering drug prices, facilitating distributed production and reducing waste.

Coordinator

UNIVERSITAT JAUME I DE CASTELLON
Net EU contribution
€ 165 312,96
Address
AVENIDA VICENT SOS BAYNAT S/N
12006 Castellon De La Plana
Spain

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Region
Este Comunitat Valenciana Castellón/Castelló
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data