Enzymatic cascade biotransformations in digitally manufactured continuous-flow bioreactors

Informations projet

FlowBioCat

N° de convention de subvention: 101064606

DOI

10.3030/101064606

Projet clôturé

Date de signature de la CE 10 Août 2022

Date de début 16 Janvier 2023

Date de fin 15 Janvier 2025

Financé au titre de

• Marie Skłodowska-Curie Actions (MSCA)

Coût total

Aucune donnée

Contribution de l’UE

€ 165 312,96

Coordonné par

UNIVERSITAT JAUME I DE CASTELLON
Spain

Periodic Reporting for period 1 - FlowBioCat (Enzymatic cascade biotransformations in digitally manufactured continuous-flow bioreactors)

Période du rapport: 2023-01-16 au 2025-01-15

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The project has yielded several key outcomes that demonstrate the potential of 3D printing and surface functionalisation for the development of efficient biocatalytic reactors. Firstly, the successful development of an epoxy-functionalised acrylate-based photocurable formulation has enabled the fabrication of high-resolution 3D-printed reactors with tailored surface properties. The ability to further modify these epoxy groups has been demonstrated, showcasing the potential for precise control over the surface chemistry of the reactor. This level of control is crucial for the creation of active surfaces that can support enzymatic activity. A significant breakthrough has been achieved with the introduction of Supported Ionic Liquids Phases (SILPs) as a chemical functionalisation method for immobilising enzymes on the reactor surface. This approach has been shown to be an efficient way to stabilise enzymatic activity, paving the way for the development of robust and reliable biocatalytic reactors. The use of SILPs has been found to enhance the stability and activity of the immobilised enzymes, making it an attractive strategy for the scale-up of biocatalytic processes.
The application of the 3D-printed bioreactor in continuous flow biotransformations has demonstrated the feasibility of this approach for the production of high-value chemicals. The reactor has been shown to facilitate efficient mass transfer and reaction kinetics, enabling the transformation of pharmaceutical commodities with high yields and selectivity, displaying an impressive enzyme stability over time. This outcome highlights the potential of 3D printing and surface functionalisation for the development of novel biocatalytic reactors that can be used in a range of applications, from pharmaceutical production to fine chemicals synthesis. Overall, the results of this project demonstrate a significant step forward in the development of efficient and scalable biocatalytic reactors and pave the way for further research and development in this area.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The successful development of devices using 3D printing to enable the efficient immobilisation of enzymes and their applications in biocatalysis in continuous flow has the potential to make a significant impact on society. By providing an alternative to metal catalysis in pharmaceutical manufacturing, this technology could lead to the production of more sustainable and environmentally friendly medicines, reducing the environmental footprint of the pharmaceutical industry. Furthermore, the adoption of continuous flow industrial production could offer numerous benefits, including increased efficiency, reduced waste, and lower costs. The potential impact of this technology extends beyond the pharmaceutical industry, with potential applications in the production of fine chemicals, food processing, and bioremediation.
Further research is needed to fully explore the possibilities of this technology, including the development of new enzyme immobilization methods, the optimization of reactor design, and the scale-up of continuous flow processes. Access to markets and finance will be crucial to the commercialization of this technology, with opportunities which may include the development of novel biocatalytic reactors, the creation of new business models for pharmaceutical manufacturing, and the establishment of new companies focused on sustainable biocatalysis.