Periodic Reporting for period 1 - greenerRPP (Greener, more sustainable platforms for high-value recombinant protein production)
Reporting period: 2022-09-01 to 2024-08-31
The overall objective of GreenerRPP research is to improve the sustainability and economic viability of industrial protein production in the bacteria Escherichia coli and Bacillus subtilis, and CHO cell lines, and to enhance both product quality and quantity with particular focus on the greener and more sustainable production of recombinant proteins.
To realise the main objectives, four interlinked Work Packages (WPs) address the key problems in this field:
WP1 aims at the development of new strategies to express target proteins in the three selected host chassis, using a series of innovations to: (i) produce such proteins in high amounts in the cytoplasm of E. coli and B. subtilis; (ii) export them to the periplasm or growth medium in E. coli and B. subtilis and (iii), secrete high amounts of biotherapeutics from CHO cell lines.
WP2 serves as the ‘strain clinic’ to improve the host strains by counteracting the stress and adaptive responses encountered under WP1.
WP3 is aimed as a “bridge” between WP1 and WP2, by integrating the acquired data with previously published data on stress responses and construct computational models that identify mitigation strategies.
WP4 is aimed at benchmarking the new strains for industrial applications.
To realise the main objectives, four interlinked Work Packages (WPs) address the key problems in this field:
WP1 aims at the development of new strategies to express target proteins in the three selected host chassis, using a series of innovations to: (i) produce such proteins in high amounts in the cytoplasm of E. coli and B. subtilis; (ii) export them to the periplasm or growth medium in E. coli and B. subtilis and (iii), secrete high amounts of biotherapeutics from CHO cell lines.
WP2 serves as the ‘strain clinic’ to improve the host strains by counteracting the stress and adaptive responses encountered under WP1.
WP3 is aimed as a “bridge” between WP1 and WP2, by integrating the acquired data with previously published data on stress responses and construct computational models that identify mitigation strategies.
WP4 is aimed at benchmarking the new strains for industrial applications.
Main achievements:
• Major progress was achieved in understanding the principles of two major protein secretion pathways in E. coli and B. subtilis, namely the Sec- and Tat pathways and secretion in CHO cell lines. This has enabled the development of new production strategies, in particular in relation to the more sustainable (greener) production of recombinant proteins.
• An enduring cooperation between the scientific and the industrial groups in GreenerRPP has been established.
• The project puts the industrial partners at the forefront of global developments, reinforcing European innovation potential in terms of growth, and sustainable production strategies.
• A new generation of researchers has been trained in the awareness of more sustainable recombinant protein production strategies.
• All DCs have been working successfully on their PhD theses.
• Major progress was achieved in understanding the principles of two major protein secretion pathways in E. coli and B. subtilis, namely the Sec- and Tat pathways and secretion in CHO cell lines. This has enabled the development of new production strategies, in particular in relation to the more sustainable (greener) production of recombinant proteins.
• An enduring cooperation between the scientific and the industrial groups in GreenerRPP has been established.
• The project puts the industrial partners at the forefront of global developments, reinforcing European innovation potential in terms of growth, and sustainable production strategies.
• A new generation of researchers has been trained in the awareness of more sustainable recombinant protein production strategies.
• All DCs have been working successfully on their PhD theses.
Importance for society:
Protein secretion systems are of great importance for society:
• Therapeutic proteins (biopharmaceuticals): Escherichia coli is used to produce over 30% of the therapeutic proteins approved to date. Many of these proteins are difficult to produce.
• Industrial enzymes, such as amylases, lipases and proteases, are usually produced in bacilli. These enzymes are used in detergent and food industries and play important roles in the daily life of many people
• Chinese hamster ovary (CHO) cell lines are an increasingly important platform for production of recombinant proteins.
Socio-economic impact:
GreenerRPP was designed to have maximum impact in terms of enhancing DC’s career prospects, provision of innovative and more sustainable protein production platforms, and stimulation of the European recombinant protein production sector.
The results from GreenerRPP have delivered several scientifically and commercially relevant findings with respect to protein production and the delivery of new sustainable production platforms. The industrial partners in GreenerRPP benefit greatly from the interactions between them and the academic partners.
Wider societal implications:
A primary aim of GreenerRPP is to train a next generation of scientists and leaders with an innovative entrepreneurial mindset, and with awareness of sustainability.
This project incorporates a series of South-East Asian Institutions as Associated Partners, and the project develops a global network with an extensive knowledge exchange.
Altogether, GreenerRPP is progressing well with respect to new concepts, technologies and novel sustainable production strategies that are of direct relevance to participant companies (DSM Food Specialties BV, Boehringer-Ingelheim, AB Enzymes).
Protein secretion systems are of great importance for society:
• Therapeutic proteins (biopharmaceuticals): Escherichia coli is used to produce over 30% of the therapeutic proteins approved to date. Many of these proteins are difficult to produce.
• Industrial enzymes, such as amylases, lipases and proteases, are usually produced in bacilli. These enzymes are used in detergent and food industries and play important roles in the daily life of many people
• Chinese hamster ovary (CHO) cell lines are an increasingly important platform for production of recombinant proteins.
Socio-economic impact:
GreenerRPP was designed to have maximum impact in terms of enhancing DC’s career prospects, provision of innovative and more sustainable protein production platforms, and stimulation of the European recombinant protein production sector.
The results from GreenerRPP have delivered several scientifically and commercially relevant findings with respect to protein production and the delivery of new sustainable production platforms. The industrial partners in GreenerRPP benefit greatly from the interactions between them and the academic partners.
Wider societal implications:
A primary aim of GreenerRPP is to train a next generation of scientists and leaders with an innovative entrepreneurial mindset, and with awareness of sustainability.
This project incorporates a series of South-East Asian Institutions as Associated Partners, and the project develops a global network with an extensive knowledge exchange.
Altogether, GreenerRPP is progressing well with respect to new concepts, technologies and novel sustainable production strategies that are of direct relevance to participant companies (DSM Food Specialties BV, Boehringer-Ingelheim, AB Enzymes).