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.
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.
Planned Impact
The CDT in Molecules to Product has the potential to make a real impact as a consequence of the transformative nature of the underpinning 'design and supply' paradigm. Through the exploitation of the generated scientific knowledge, a new approach to the product development lifecycle will be developed. This know-how will impact significantly on productivity, consistency and performance within the speciality chemicals, home and personal care (HPC), fast moving consumer goods (FMCG), food and beverage, and pharma/biopharma sectors.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.
