ConBioChem: Continuous bio-production of commodity chemicals

Lead Research Organisation: University of Cambridge
Department Name: Biochemistry


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


10 25 50
Description Continous biprocesses for chemicals production
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Change in policy of chemicals manufacturers towards continuous bioprocesses and training in metabolic modelling, synthetic biology, and chemostat culture
Description Continuous protein production
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Impact Our work on the continuous production of recombinant proteins in the industrial yeast Pichia pastoris has completely changed the attitude of industry to the continuous production of therapeutic antibodies and platform chemicals,
Title Flexible Nets 
Description Mathematical models that combine predictive accuracy with explanatory power are central to the progress of systems and synthetic biology, but the heterogeneity and incompleteness of biological data impede our ability to construct such models. Furthermore, the robustness displayed by many biological systems means that they have the flexibility to operate under a range of physiological conditions and this is difficult for many modeling formalisms to handle. Flexible nets (FNs) address these challenges and represent a paradigm shift in model-based analysis of biological systems. FNs can: (i) handle uncertainties, ranges and missing information in concentrations, stoichiometry, network topology, and transition rates without having to resort to statistical approaches; (ii) accommodate different types of data in a unified model that integrates various cellular mechanisms; and (iii) be employed for system optimization and model predictive control. 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact Radical new method of modelling biological systems whcih also allows real-time control of bioprocesses.