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Systems engineering of cell factories almost doubles output and offers a sustainable alternative to producing chemicals from fossil-fuel

Engineers from The University of Warwick’s Integrative Synthetic Biology Centre and Imperial College London’s Department of Bioengineering have unveiled how to engineer microbial ‘cell-factories’ to boost the manufacture of high-value chemicals that are used in everyday products like domestic goods, clothes and food.

To date cell-based systems have been less efficient than existing petrochemical processes due to natural constraints within living cells. However, through computational modelling, the team has demonstrated that simple refinements of existing methods can boost production nearly two-fold.

Engineering living cells (such as bacteria and yeasts) to produce chemicals has the potential to create a greener chemicals industry. This could replace carbon-intensive petrochemical-based systems with bio-based cell factories that convert cheap and sustainably sourced feedstocks into valuable chemicals.

Dr Alexander Darlington, Royal Academy of Engineering Research Fellow and Assistant Professor at The University of Warwick, said “Our research offers strategies for designing bacteria that are easier to implement than those currently considered state-of-the-art. We tested around 500 different control mechanisms, and found two that were new to research, which offers a clear pathway toward more efficient bio-based synthesis of chemicals. This will enable the sustainable manufacture of everything from drugs to plastics, products we use every day”

The team found that designs that reprogramme cells to deprioritise growth, rather than

solely synthesise the product, enable the highest production capabilities. Designs that deactivated growth later, after allowing cells to grow to large populations, were predicted to reach higher production levels in the shortest times, while those that also increased nutrient uptake were predicted to achieve even higher outputs.

The study also considered the econometrics of production – the modelling of economic data – which points to manufacturers designing their systems to either optimise for higher productivity (faster production), to maximise the amount produced in the shortest time if the chemical market is high, or higher yield (more product from the same input), if the feedstock is expensive or the chemical market value is low.

Dr Ahmad Mannan, postdoctoral research associate at Imperial College London, said “As an engineer, I want to minimise the negative impact our living has on others and the environment and achieve sustainable and renewable chemical production – and bacteria can facilitate that. With expertise at the interface between mathematics, molecular biology and synthetic biology, we are uncovering simple rules that should enable us to harness nature’s capabilities and achieve economically viable chemical production.”

The team are now piloting these new design principles in the laboratory to give industry partners the confidence they need to incorporate these methods into their R&D programmes. The ability to significantly boost the chemical production of bacteria is a massive step towards scaling-up of bio-based chemical manufacturing. With 14% of all greenhouse gases coming from fossil fuel chemical synthesis, cell factories offer an alternative which could help the UK government meet the target of net zero by 2050.

The full paper is published in Nature Communications volume 16, Article number: 279 (2025).

DOI: 10.1038/s41467-024-55347-y 

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Notes to editor

Alexander P. S. Darlington is a receipt of a Royal Academy of Engineering Research Fellowship (RF/202021/20/270) and his group has received funding from the EPSRC (EP/Y00342X/1, EP/X039587/1) and the UKRI Technology Mission Fund via the BBSRC (BB/Y007603/1). Ahmad A. Mannan and Declan G. Bates were funded by the BBSRC (BB/M017982/1).

Ahmad A. Mannan and Reiko J. Tanaka, Imperial College London are funded by Innovate UK and the European Union EIC Pathfinder (SKINDEV ‘Skin microbial devices’, 101098826).

The UK is a world leader in engineering biology with Engineering Biology sector having a total turnover of £108.3bn a year but getting biobased chemicals to be cost competitive with petrochemicals remains a challenge, this research contributes to addressing this and once experimentally validated could be a step change in the way we design bioproduction systems.

The University of Warwick is one of the UK’s leading universities, marking its 60th anniversary in 2025. With over twenty-eight thousand students from 147 countries, it's currently ranked 9th in the UK by The Guardian University Guide. It has an acknowledged reputation for excellence in research and teaching, for innovation, and for links with business and industry. The recent Reearch Excellence Framework classed 92% of its research as ‘world leading’ or ‘internationally excellent’. The University of Warwick was awarded Midlands University of the Year by The Times and Sunday Times.

University of Warwick press officer Heather Holve is available on + 44 (0) 7803 052441 or heather.holve@warwick.ac.uk