€2.4M European ERA CoBioTech Project Success for CBMNet

We are proud to announce that a CBMNet led proposal to the First transnational Call for research projects within the framework of the ERA-NET Cofund on Biotechnologies (ERA CoBioTech) “Biotechnology for a Sustainable Bioeconomy”, has been successful.

Developed through CBMNet and led by CBMNet Management Board member Dr Alan Goddard, with CBMNet Co-Director Professor Gavin Thomas as co-investigator, ‘MEmbrane Modulation for BiopRocess enhANcEment’ (MEMBRANE), will deliver bespoke robust industrially-viable cell factory strains, engineered to overcome current bioprocess and production bottlenecks, accelerating the commercialisation of two significant industrial bioprocesses. Implementation of this project will significantly reduce production costs and environmental impact for two companies, increasing product sustainability.

“We are delighted with this EU funding, both as further recognition of CBMNet-led proposals bearing fruit, but also that the EU can recognise that there is much under-explored biology around the microbial cell membranes that could be exploited in industrial biotechnology and bioenergy”

Professor Gavin Thomas, CBMNet Co-Director, University of York

This 36-month project sees five leading research institutes (Aston University, University of York, Forschungszentrum Jülich, IATA-CSIC and Groningen) and two large industry partners (Lallemand and Pakmaya), across five countries, collaborate, and validate at pilot scale, engineered robust cell factories (yeast and Propionibacterium) that overcome existing toxicity challenges, improve efficiency and allow their effective commercialisation. The strategies developed within this project will be applicable across the sector to facilitate rational strain engineering with far-reaching benefits.

The multinational multidisciplinary team are all CBMNet members and combines skills in lipidomics, proteomics, transcriptomics, biophysics, MD simulations, strain engineering, high throughput screening and commercial process and product development. The collaborative, integrated and iterative approach maximises impact; it would be impossible for any one partner to conduct this project alone and success is contingent upon the expertise of all partners.

“CBMNet was my first exposure to Industrial Biotechnology and I feel that I have had tremendous support from the network since its inception, both in terms of people I have met, networking events and conferences, and funding opportunities available. The underpinning ideas for our successful ERA CoBioTech proposal emerged from a number of CBMNet-funded projects and fruitful conversations with both academics and industrial partners. The consortium was built through CBMNet, utilising existing connections and also by leveraging the EU-wide reach of CBMNet to recruit relevant academic and industrial partners to work on a project of mutual interest. CBMNet has been incredibly supportive throughout the process”

Dr Alan Goddard, Aston University

The global economy has an unsustainable dependence on fossil raw material with demand for raw material inputs to industry growing steadily. Concerns about environmental sustainability are becoming more acute; thus, alternatives to traditional, fossil-fuel based chemical production are urgently required. Cell factories, which use microorganisms to produce materials from renewable biomass, are an attractive alternative, and an increasing number of platform chemicals are being produced at industrial scale using engineered microorganisms. These are expected to have a transformative impact in industrial biotechnology, but, first, we must meet the challenges of designing and optimizing high-yield cell factory strains that can produce commercially viable amounts of product. One reason for poor product output is that the production conditions are ultimately toxic to the producing cells. In addition to damage to intracellular components such as enzymes, the lipid cell membrane and associated proteins are vulnerable to biomolecules e.g. ethanol and propionate, as well as to physical parameters during production such as osmotic stress, pH, and temperature. An approach whereby membranes can be “tuned”, in terms of their lipid and protein content, to become more resistant to stresses brought about by toxicity would revolutionise the field. Additionally, expression of efficient membrane transporters to export ‘toxic’ products can mitigate intracellular damage. These approaches will ultimately enable production of higher concentrations of the desired molecules or cells making the bioprocesses more efficient, increasing product yield, reducing cost, and help to drive the move away from fossil-based raw materials. An adoption of such “green” processes and avoidance of depletion of non-renewable carbon sources will bring huge social and environmental benefits. Products and processes which  are currently economically unviable due to toxicity can be rendered profitable by even small increases in the resistance of strains and concomitant yield increases.

The project is divided into seven interconnected, iterative work packages (WPs) with a well-established build-test-analyse approach. Initial analysis of –omics data will identify key alterations in membrane protein and lipid content of both microbes subjected to stresses associated with bioproduction and those strains known to be somewhat resistant to such stresses (WP1). In vitro and in silico approaches will be used to rapidly delineate the roles of these alterations and rationally design more resistant membranes (WP2). Using synthetic biology and strain evolution approaches, we will alter the membrane composition of microbes to reflect the “optimal” membranes determined in WP2 (WP3). Optimal strains will be identified in a high throughput manner and subjected to large-scale testing to ensure that the changes made translate to the industrial setting (WP4). Following this, another iteration of the cycle will further optimise the strains. WP5 will evaluate the environmental and social sustainability of the innovative production processes and the final products. WP6 will develop and implement a strategy for the dissemination and exploitation of research results to different stakeholders. WP7 involves consortium management, project governance, communication activities and administrative oversight to ensure maximum impact of the project.

Project Partners:

Dr Alan Goddard, Aston University

Dr Gavin Thomas, University of York

Dr Amparo Querol, Consejo Superior de Investigaciones Científicas (CSIC), Institute of  Agrochemistry and Food Technology

Dr Stephan Noack, Forschungszentrum Jülich

Prof Siewert-Jan Marrink, The University of Groningen

Dr Mustafa Turker, Pakmaya

Dr Jose Heras, Lallemand

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