17-ERACoBioTech - MEmbrane Modulation for BiopRocess enhANcEment - MeMBrane

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


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.


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Ayub H (2022) Membrane Protein Production in the Yeast P. pastoris. in Methods in molecular biology (Clifton, N.J.)

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Broadbent L (2022) Detergent-Free Membrane Protein Purification Using SMA Polymer. in Methods in molecular biology (Clifton, N.J.)

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Depping P (2022) Heterologous Expression of Membrane Proteins in E. coli. in Methods in molecular biology (Clifton, N.J.)

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Routledge SJ (2019) Liposomes as models for membrane integrity. in Biochemical Society transactions

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Vaitsopoulou A (2022) Membrane Protein Production in Insect Cells. in Methods in molecular biology (Clifton, N.J.)

Title Megson video 
Description We co-wrote a song with the band Megson which is accompanied by a commissioned animated video. The video is available on YouTube. 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2020 
Impact The video has been viewed over 1,200 times on YouTube and over 10,000 times on Facebook. Comments indicate that this has been picked up as a school resource nationally. 
URL https://www.youtube.com/watch?v=bxc3DLASUrw
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/
Title SuperYeast Book 
Description We have written an illustrated book for school-aged children relating to the overarching concept of the SuperYeast project. It will soon be available via our website as a pdf. 
Type Of Art Creative Writing 
Year Produced 2021 
Impact None yet - still to be released. 
Description In this project, we were exploring the effect of stress on the thin membrane that surrounds all cells. In our case, we were really interested in the effect of molecules made biotechnologically, specifically ethanol, weak acids and drugs. In this project, we have developed a molecular model of how the cell membrane responds to ethanol stress and coupled this to microbiological work showing that the membrane components we would predict from our models to be protective are, indeed, found more commonly in yeast cells that as ethanol stressed. In order to improve the yeast strains to tolerate higher ethanol levels (needed as climate change results in more sugar in grapes and hence more ethanol produced) we undertook lipid, protein and genetic analysis of the strains. This has revealed targets for strain improvement and, through a combination of lab-scale evolution, and selective breeding of yeast strains, we have developed hybrids that are more ethanol tolerant and are now being tested at industrial scale. In a related element of the project, we have used our understanding of the effect of weak acids on bacteria to design a fermentation process to optimise production of this platform chemical. This as involved careful control of fermentation conditions and an understanding of the role the cell membrane plays here. Finally, we have developed a methodological approach for improvement of bacterial tolerance to drugs made through fermentation. Through a combination of modelling, in vitro work and microbiology, we have identified that supplementation of the strains with membrane components allows a significant increase in yield of toxic compounds.
Exploitation Route We anticipate the approaches we have developed here will be widely applicable across the biotechnological sector as the cell membrane represents the major target of stress in many of these processes.
Sectors Manufacturing, including Industrial Biotechology

Description Our strains are currently being tested in scale up processes at industrial level. We await the outcomes of these.
First Year Of Impact 2021
Sector Manufacturing, including Industrial Biotechology
Impact Types Economic

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 A mass spectrometry centre for the analysis of glycerolipids, glycerophospholipids and sphingolipids, and their lipid oxidation products
Amount £637,476 (GBP)
Funding ID BB/S01943X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2019 
End 06/2020
Description Biotechnological Knowledge Transfer in a Pandemic-affected World
Amount £24,614 (GBP)
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2021 
End 04/2022
Description UKRI Citizen Science Exploration Grant
Amount £19,765 (GBP)
Funding ID BB/T018739/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2020 
End 06/2020
Title Dataset for Analysis of lipid composition reveals mechanisms of ethanol tolerance in the model yeast Saccharomyces cerevisiae 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL https://researchdata.aston.ac.uk/id/eprint/495
Description HBVNet BIV 
Organisation Corteva Agriscience
Country United States 
Sector Private 
PI Contribution We were investigating the effect of membrane toxicity of a high value chemical on a bacterial membrane. This made use of the techniques developed in MeMBrane.
Collaborator Contribution Our partners provided strains and expertise in the manufacture of the high value chemical.
Impact None.
Start Year 2020
Description UKRI Citizen Science Award 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution We are the scientific leads on the UKRI citizen science grant.
Collaborator Contribution York provide expertise in citizen science projects and evaluation of such projects.
Impact None
Start Year 2020
Description FZJ Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact FZJ open day in German highlighting the entire MeMBrane project. 28,000 visitors attended with the opportunity to speak to staff and students about the project.
Year(s) Of Engagement Activity 2020
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/