Title: ENZYMATIC CASCADE BIOTRANSFORMATIONS IN DIGITALLY MANUFACTURED CONTINUOS-FLOW BIOREACTORS
Acronym of the project: FLOWBIOCAT
Funding entity: HORIZONTE EUROPA
Modality: MARIE SKLODOWSKA CURIE ACTIONS
Entity code: Project 101064606
UJI accounting code: 22I413
Principal researchers: 
  1. Gianluca Palmara
Dates: 2023-01-16 to 2025-01-15
Involved researchers: 
  1. Victor Sans Sangorrin
Summary/Abstract: 
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