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

Publications

10 25 50
 
Description Synthetic biology strategies have been combined with fermentation cultivation strategies, enabling continuous bio-manufacturing producing a favourable techno-economic outcome. This novel, blended approach has further enhanced the cost competitiveness of sustainable processing when compared to petrochemical alternatives.
Exploitation Route Continuous fermentation allows for significant operating cost savings from a techno-economic perspective. The exemplified technology would find application in a number of different sectors seeking to produce biofuels / biochemicals through sustainable processing.
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 CHAIN 
Organisation Chain Biotech
Country United Kingdom 
Sector Private 
PI Contribution Nottingham is the lead partner on ConBioChem
Collaborator Contribution Industrial Partner in ConBioChem
Impact None yet
Start Year 2016
 
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 Green Biologics 
Organisation Green Biologics
Country United Kingdom 
Sector Private 
PI Contribution Nottingham is a collaborator on HIPHOP (led by Green Biologics), lead partner on ConBiochem and collaborator on Detox.
Collaborator Contribution Green Biologics led HIPHOP and are industrial partners on Detox and ConBioChem, building on a pre-2006 direct funded studentship
Impact No publications yet
 
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 Lucite 
Organisation Lucite International
Department Lucite International UK 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 Lucite 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