A new generation of microbial expression hosts and tools for the production of biotherapeutics and high-value enzymes

The ‘SECRETERS’ partnership aims to bring about a step change in the production of recombinant proteins, particularly Biotherapeutics and Industrial Enzymes. Both are critical products for the EU biotechnology sector, with combined markets in excess of $140 billion p.a.; the former are essential for the treatment of major diseases whereas the latter permeate every aspect of our daily life. Many proteins in these categories pose severe problems in production, especially disulphide-bonded proteins and new format 'difficult-to-express' proteins. SECRETERS will train a team of 15 ESRs to develop a new generation of super-producing microbial production hosts, including Escherichia coli , Bacillus subtilis and the yeast Pichia pastoris . The project capitalizes on a series of recent innovations and involves close collaboration between 5 academic Beneficiaries with expertise in redox chemistry, synthetic biology and protein expression, and 5 non-academic Beneficiaries, who include some of the world's premier biotherapeutic and industrial enzyme companies. It will enable the biotherapeutics industry to produce challenging medicines at lower costs, resulting in new drugs and wider patient access, and allow the enzymes industry to deliver a range of powerful new products. SECRETERS will equip ESRs with the interdisciplinary and intersectoral skills required to thrive in these industries, with quality assurance systems embedded throughout the programme and a commitment to a wide-ranging dissemination/outreach programme. Based on a responsible innovation approach, with clear foci on research and entrepreneurial training, SECRETERS will deliver a team of highly trained scientists, poised to engage in some of Europe's most important biotechnology sectors.

Research workplan and outputs. WP1 will use new strategies to produce disulphide-bonded recombinant proteins in bacteria and P. pastoris. WP2 (the ‘strain clinic’) will improve the host strains by counteracting stress and adaptive responses, which set limits on productivity. WP3 will inform and bridge WPs 1 and 2 by integrating acquired data on the stress responses and constructing computational models that identify mitigation strategies. These will be fed back to WP1 and WP2 for validation and design of next-generation chassis. WP4 will pinpoint demands that are only evident in the industrial setups and feed them to WP3. WP4 will also validate the new strains for industrial application.