17-ERACoBioTech - MEmbrane Modulation for BiopRocess enhANcEment - MeMBrane

Lead Research Organisation: Aston University
Department Name: Sch of Life and Health Sciences

Abstract

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.
This 36-month project sees five leading research institutes (Aston, York, FZJ, 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 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.

Technical Summary

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.

Planned Impact

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.

Publications

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Title Microstrike 
Description We created a board game to be distributed to schools along with accompanying fact sheets. The game is called Microstrike. 
Type Of Art Artefact (including digital) 
Year Produced 2019 
Impact Distributed to two schools so far. 
URL https://www.membrane.org.uk/news-and-events/
 
Description Experimental techniques for studying proteins and lipids in biological membranes
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
URL https://www.biochemistry.org/Events/tabid/379/Filter/64/MeetingNo/TD019/view/Conference/Default.aspx
 
Description Lichfield Schools Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 100 students attended the Lichfield Science and Engineering Society annual Schools' lecture. We discussed biotechnology and the impact of GM on the environment and society. The feedback was excellent and students appeared genuinely interested in the topic and ensuing debate.
Year(s) Of Engagement Activity 2019
URL http://www.lses.org.uk/education-support/
 
Description YorNight 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Researchers from York ans Aston gathered at Kings Manor on 17th Nov 2018 to tell the public about their research. The event was aimed at getting young people interested in STEM subjects and many of the exhibits were interactive and family oriented. MeMBrane was represented on the Marvellous Microbes stand with the first outing of Microstrike, the bug based board game, and 'Ask a scientist', an opportunity for the public to ask any questions to research scientists. Answers to questions from the public are answered on https://padlet.com/joyce_bennett/AskAScientist. The public had the opportunity to swab their own microbiome and see what grew here: www.biologybex.wordpress.com/marvellous-microbes. We also raced bug powered boats, using butanol to exemplify a biofuel that can be made in bacteria and demonstrated how we can target specific molecules created by bacteria to prevent body odour.
Year(s) Of Engagement Activity 2018
URL https://www.membrane.org.uk/news-and-events/