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HEIndividual fellowship2023–2025

FlowBioCat · Enzymatic cascade biotransformations in digitally manufactured continuous-flow bioreactors

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-01-16 → 2025-01-15
EU contribution
€165,313
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

Enzymatic cascade biotransformations in digitally manufactured continuous-flow bioreactors

Drug discovery and development in pharmaceutical industry has experienced a revolution in recent years, driven by the application of biocatalysis in industrial biotechnology. By harnessing the power of enzymes as (bio)catalysts, synthetic chemists can generate complex molecular structures while avoiding costly and time-consuming protection and deprotection steps. However, the widespread adoption of biocatalytic processes is hindered by several key challenges, including high costs, particularly when cofactors are required, limited substrate tolerance and productivity, and difficulties in scaling up. Recent advances in enzyme immobilisation and continuous flow technology offer a promising solution to these limitations. By immobilising enzymes, their performance and recyclability can be significantly enhanced, while continuous flow can mitigate issues such as low productivity and substrate inhibition. Traditional packed bed reactors have been the most common method for enzyme immobilisation, but their limitations in flow rates and mixing capabilities can lead to inefficient conversion and batch-like reaction conditions. This project aims to address these challenges through the design and manufacture of 3D printed reactors that combine optimised mixing at low flow rates with tailored surface modification techniques using ionic liquids for stable biocatalyst preparation and increased active sites. The use of 3D printing enables the creation of complex geometries in a variety of materials, tailored to optimise enzyme stability. By integrating chemical engineering and biocatalysis, this project seeks to develop more efficient biotransformations in flow, facilitate easy and effective enzyme immobilisation, and promote sustainable development in industrial biotechnology.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

Participants

  • UNIVERSITAT JAUME I DE CASTELLON · Castellon De La PlanaCoordinatorSpain

Links

Data: CORDIS, © European Union