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Systems engineering of cell factories almost doubles output, offering a sustainable fossil-fuel alternative

Engineers from The University of Warwick's Integrative Synthetic Biology Center 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 modeling, 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 chemical 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 offer 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 reprogram cells to deprioritize growth, rather than solely synthesize 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 modeling of economic data—which points to manufacturers designing their systems to either optimize for higher productivity (faster production), to maximize 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.

The findings are in the journal Nature Communications.

Dr. Ahmad Mannan, postdoctoral research associate at Imperial College London, said "As an engineer, I want to minimize 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 programs. 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 U.K. government meet the target of net zero by 2050.