ConBioChem: Continuous bio-production of commodity chemicals
Lead Research Organisation:
University of Nottingham
Department Name: Faculty of Engineering
Abstract
The current slump in oil prices should not lead us to ignore the fact that, in the future, an ever-increasing proportion of the fuels and chemicals, required for everything from jumbo jets to toy elephants, will need to come from renewable resources. This means a huge expansion of the fermentation industry, and the cost of the required manufacturing plant will rapidly become unaffordable. The solution is to move from performing fermentations batchwise (like manufacturing cars one at a time) to continuous processes (like an automobile production line). This major change presents a number of challenges in engineering production microbes, and in designing and controlling the industrial processes in which they operate. This project aims to produce a pipeline that will meet all of these challenges in an integrative manner. It will result in stable and robust production microbes in which there is an optimal balance between the growth of the process microorganism and formation of the industrial product that it generates. The new microbes will be exploited in new continuous processes, and process controls will be developed in which the microbe is 'rewarded' with nutrients for generating high levels of the industrial product. Such a 'control by incentives' strategy will, in itself, contribute to the stability of the production organism. The environmental impacts of the new processes will be assessed to ensure that they are cleaner and greener than the chemical processes that they are replacing. Lastly, the costs of building new factories to manufacture the chemicals will be assessed, together with the costs of operating them, to ensure that the new continuous bio-manufacturing processes will be profitable for UK companies.
Technical Summary
This ambitious, multidisciplinary project will establish generic design procedures to underpin the introduction of continuous bio-manufacturing processes for commodity/platform chemicals and added value intermediates. Crucial improvements in operational stability will be delivered through Synthetic Biology, to construct genetically stable chassis strains. Metabolic modelling will be used to design rational strain engineering and processing strategies, to divert cellular metabolism away from growth and towards product formation, to deliver critical improvements in product yields. The metabolic models will be integrated into multiscale models, involving reactor and process models and LCA, to enable seamless, integrated design of both the organisms and the processes, so that both will operate synergistically for maximal commercial benefit and sustainability. Success will be measured through technoeconomic analysis to deliver commercially relevant design approaches.
Planned Impact
As described in proposal submitted to IUK
Organisations
- University of Nottingham, United Kingdom (Lead Research Organisation)
- EPSRC, United Kingdom (Co-funder)
- University College London, United Kingdom (Collaboration)
- University of Cambridge (Collaboration)
- Ingenza Ltd, United Kingdom (Collaboration, Project Partner)
- Centre for Process Innovation (CPI) (Collaboration)
- Mitsubishi Chemical Co Ltd (Collaboration)
- Lucite International UK Ltd, United Kingdom (Project Partner)
- UK-CPI (Project Partner)
- Green Biologics Limited, United Kingdom (Project Partner)
- Chain Biotechnology Ltd (Project Partner)
Publications

Bommareddy RR
(2020)
A Sustainable Chemicals Manufacturing Paradigm Using CO2 and Renewable H2.
in iScience

Julez J
(2019)
Modelling, analyzing and controlling hybrid systems by Guarded Flexible Nets
in Nonlinear Analysis: Hybrid Systems

Julvez J
(2020)
Steady State Analysis of Flexible Nets
in IEEE Transactions on Automatic Control

Júlvez J
(2018)
Handling variability and incompleteness of biological data by flexible nets: a case study for Wilson disease.
in NPJ systems biology and applications


Meng F
(2019)
Challenges in Quantifying Greenhouse Gas Impacts of Waste-Based Biofuels in EU and US Biofuel Policies: Case Study of Butanol and Ethanol Production from Municipal Solid Waste.
in Environmental science & technology

Rodgers S
(2021)
Reconciling the Sustainable Manufacturing of Commodity Chemicals with Feasible Technoeconomic Outcomes : Assessing the investment case for heat integrated aerobic gas fermentation
in Johnson Matthey Technology Review

Vaud S
(2021)
Engineering improved ethylene production: Leveraging systems biology and adaptive laboratory evolution.
in Metabolic engineering
Description | Stable continuous fermentation has been exemplified using citramalate production as a case study without resorting to antibiotic selection pressure or the use of inducers. The novel exploitation of phosphate limitation, addiction systems and constitutive promoters meaningfully contributes to more feasible techno-economic outcomes in biomanufacturing. |
Exploitation Route | The outcomes for ConBioChem have led to a successful Prosperity Partnership (EP/V038052/1) with Mitsubishi Chemical (previously Lucite International). |
Sectors | Agriculture, Food and Drink,Chemicals,Energy,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Description | Materials and Manufacturing |
Amount | £1,601,686 (GBP) |
Funding ID | 103761 |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 01/2018 |
End | 12/2020 |
Description | Scale-up and techno-economic validation (Biomonomer) |
Amount | £764,680 (GBP) |
Funding ID | Innovate UK 105044 |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 03/2021 |
Description | CPI |
Organisation | Centre for Process Innovation (CPI) |
Country | United Kingdom |
Sector | Private |
PI Contribution | Nottingham is the Lead partner for ConBioChem and Collaborator on Detox |
Collaborator Contribution | Industrial partner for ConBioChem and Detox |
Impact | None yet |
Start Year | 2016 |
Description | Ingenza |
Organisation | Ingenza Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Nottingham were partners in the P2P project with Ingenza and Lucite. We also lead the ConBioChem IB catalyst project, for which Ingenza are an industrial partner. We are partners in the Detox IB catalyst project, for which Ingenza are an industrial partner. Ingenza act as industrial hosts for CASE industrial experience placements for our Lucite-sponsored CASE studentships, since they have biotechnology laboratories and Lucite do not. |
Collaborator Contribution | Ingenza and Nottingham are partners within the Lucite project to develop bio-based manufacturing of methylmethacrylate. Ingenza were the lead partner for the P2P project. Ingenza act as industrial hosts for CASE industrial experience placements for our Lucite-sponsored CASE studentships, since they have biotechnology laboratories and Lucite do not. Ingenza are industrial partners in the ConBioChem IB catalyst project (which Nottingham leads) and in the Detox IB catalyst project (in which Nottingham is a partner). |
Impact | GR Eastham, DW Johnson, I Archer, R Carr, J Webb, G Stephens (2015). A Process for Production of Methacrylic Acid and Derivatives Thereof. WO2015022496 Multidisciplinary: Chemistry, microbiology, biochemistry, molecular biology, biotechnology |
Start Year | 2013 |
Description | Mitsubishi Chemical UK |
Organisation | Mitsubishi Chemical Co Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Nottingham works with Lucite to develop metabolically engineered microorganisms for bio-based methymethacrylate production. We also develop fed-batch and continuous bioprocesses, and methods to solve problems with product toxicity. The work has been done through 7 CASE studentships (Lucite), 2 small projects (Lucite), the P2P grant and our IB catalyst projects, Detox and ConBioChem. |
Collaborator Contribution | Mitsubishi Chemical (previously Lucite International) aim to develop a bio-based route to manufacture methylmethacrylate. Lucite have funded 7 CASE studentships, 2 small projects, have collaborated on the P2P grant and are partners on our IB catalyst projects, Detox and ConBioChem. |
Impact | GR Eastham, G Stephens, A Yiakoumetti (2016). Process for the biological production of methacrylic acid and derivatives thereof. WO2016185211 A1 L Rossoni, SJ Hall, G Eastham, P Licence and G Stephens (2015) The putative mevalonate diphosphate decarboxylase from Picrophilus torridus is in reality a mevalonate-3-kinase with high potential for bio-production of isobutene. Applied and Environmental Microbiology 81, 2625-2634 doi: 10.1128/AEM.04033-14 GR Eastham, DW Johnson, I Archer, R Carr, J Webb, G Stephens (2015). A Process for Production of Methacrylic Acid and Derivatives Thereof. WO2015022496 Multidisciplinary: Chemistry, Biotechnology, Microbiology, Biochemistry, Molecular Biology |
Start Year | 2011 |
Description | UCL |
Organisation | University College London |
Department | UCL Genomics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Nottingham is the lead partner for ConBioChem |
Collaborator Contribution | Collaborator for ConBioChem |
Impact | None yet Multidisciplinary: Microbiology, engineering, molecular biology, biotechnology |
Start Year | 2016 |
Description | University of Cambridge |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Nottingham is Lead partner on ConBioChem and collaborators on Detox projects |
Collaborator Contribution | Collaborators on ConBioChem and Detox |
Impact | None yet |
Start Year | 2016 |
Description | Festival of Science and Curiosity |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Festival of Science and Curiosity - outreach event engaging the general public in the opportunities associated with biotechnology and sustainable processing. |
Year(s) Of Engagement Activity | 2020 |
Description | International Women's Day Event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | International Women's Day Event - engagement event with the general public on the opportunities associated with biotechnology and sustainable processing. |
Year(s) Of Engagement Activity | 2020 |
Description | Science in the Park |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Science in the Park - outreach event engaging the general public in the opportunities associated with biotechnology and sustainable processing. |
Year(s) Of Engagement Activity | 2020 |
Description | Wonder |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Wonder outreach event, engaging with the general public on the opportunities associated with biotechnology and sustainable processing. |
Year(s) Of Engagement Activity | 2019 |