Comparative Analysis of Dynamic Control Circuit Designs for Bacterial Chemical Production
Explanation:
This figure demonstrates how different control circuit designs influence the efficiency of bacterial chemical production systems. The Pareto front in panel (a) shows the best achievable trade-offs between yield and productivity for each control strategy. Dynamic circuits that balance both host growth and synthesis (red) outperform those with more limited focus. Panel (b) highlights critical parameters for the top-performing design, indicating that specific tuning of transcription rates and induction timing can significantly boost productivity. This insight provides actionable guidelines for designing optimized microbial systems.
Engineering Bacteria for Chemical Production: Study Boosts Efficiency and Sustainability
Researchers from the University of Warwick and Imperial College London have demonstrated new methods for engineering microbial "cell factories" to produce valuable chemicals more efficiently, potentially offering a greener alternative to petrochemical processes. The study, recently published in Nature Communications, outlines computational strategies that nearly double production rates of chemicals used in pharmaceuticals, plastics, and food production.
Dr. Alexander Darlington, a Royal Academy of Engineering Research Fellow at the University of Warwick, and Dr. Ahmad Mannan, a postdoctoral researcher at Imperial College London, led the research. The team employed a "host-aware" computational framework to analyze how cellular resources are shared between growth and chemical production. By optimizing genetic designs that prioritize production over growth at strategic times, they uncovered simple yet effective ways to boost output while reducing resource waste.
Key Findings and Methods
The study highlights two primary strategies:
- Two-Stage Production Models: Allowing bacterial populations to grow before switching to a chemical production phase increased output and efficiency.
- Nutrient Uptake Optimization: Enhancing the expression of nutrient transporters significantly improved productivity without requiring major changes to existing genetic designs.
The researchers evaluated hundreds of potential control mechanisms, identifying a subset that balanced high production with sustainable resource use. The findings suggest that these methods could guide the engineering of bacteria to produce a range of high-value chemicals economically and at scale.
Impact on Sustainability Goals
With petrochemical processes contributing approximately 14% of global greenhouse gas emissions, bio-based production offers a viable path toward sustainable manufacturing. By converting inexpensive, renewable feedstocks into essential products, this research supports efforts to reduce reliance on fossil fuels and aligns with goals for achieving net-zero emissions.
Institutional Contributions and Background
This collaboration leveraged expertise across synthetic biology, bioengineering, and computational modeling. The University of Warwick's Integrative Synthetic Biology Center and Imperial College London's Department of Bioengineering provided a strong foundation for the work. The researchers built on prior studies of dynamic metabolic regulation and resource optimization in bacteria.
Dr. Mannan’s earlier work includes dynamic control mechanisms for bacterial metabolic states, while Dr. Darlington has contributed to computational models predicting cellular resource allocation. Their combined efforts reflect a growing emphasis on applying engineering principles to biological systems for practical applications.
Future Directions
The team plans to pilot these methods in laboratory settings, collaborating with industry partners to scale up production. This step will be crucial for determining the economic viability of these approaches and integrating them into commercial chemical manufacturing processes. Additionally, their findings may inform broader applications, from drug synthesis to the production of bio-based materials.
The full research article, titled "Design principles for engineering bacteria to maximize chemical production from batch cultures," is available in Nature Communications (DOI: 10.1038/s41467-024-55347-y).
Researchers from the University of Warwick and Imperial College London have made a breakthrough in engineering microbial "cell-factories" that could help create a more sustainable chemical industry. Here are the main findings:
1. The team discovered new ways to boost the production efficiency of bacteria-based chemical manufacturing, achieving nearly double the output of previous methods.
2. Through testing about 500 different control mechanisms, they identified two novel approaches:
- Reprogramming cells to deprioritize growth in favor of product synthesis
- Delaying growth deactivation until after larger cell populations develop
3. The research provides manufacturers with two optimization strategies:
- Higher productivity (faster production) for high-value chemical markets
- Higher yield (more efficient input-to-output ratio) for expensive feedstocks or lower-value markets
4. This advancement is significant for sustainability because:
- It could help replace carbon-intensive petrochemical processes
- It offers a way to produce everyday products (drugs, plastics, domestic goods) more sustainably
- It could contribute to reducing the 14% of greenhouse gases that come from fossil fuel chemical synthesis
The researchers are now testing these principles in laboratory settings to encourage industry adoption, which could help support the UK's goal of reaching net zero emissions by 2050.
This study is about engineering bacteria to maximize the production of chemicals in batch cultures. The researchers used a computational model that takes into account the competition for resources within the host cells, such as ribosomes and metabolites.
Research objectives and hypotheses:
The main objectives were to:
1. Understand how to select bacterial strains with the right balance of growth and synthesis rates to maximize productivity and yield from batch cultures.
2. Develop genetic circuits that can switch the cells from a high-growth to a high-synthesis state to further improve production performance.
Methodology:
The researchers developed a multi-scale mathematical model that captures the dynamics of cell growth, metabolism, enzyme expression, and product synthesis. They then used multi-objective optimization methods to find the optimal enzyme expression levels and genetic circuit designs to maximize productivity and yield.
Results and findings:
1. Strains with lower growth but higher synthesis rates can achieve near-optimal productivity and yield.
2. Genetic circuits that induce a switch from high-growth to high-synthesis state can further improve performance.
3. The key design principle is to engineer the circuit to redirect the host's metabolism from growth to product synthesis, rather than just activating the synthesis pathway.
4. Increasing the expression of nutrient transporters can also improve performance.
Discussion and interpretation:
The findings suggest that it is possible to select production strains based on their growth and synthesis rates, without the need to directly test for productivity and yield. The two-stage genetic circuits can achieve higher performance by redirecting the host's metabolism, even with a simple circuit design.
Contributions to the field:
This study provides important insights into the design principles for engineering microbial cell factories to maximize chemical production. The computational framework and optimization methods can be applied to a wide range of microbial production systems.
Achievements and significance:
The study shows that it is possible to achieve high productivity and yield in batch cultures by carefully engineering the expression of host and production enzymes, as well as the genetic circuits controlling them.
Limitations and future work:
The study uses a simplified model of metabolism and does not consider all the potential complexities of real biological systems. Future work could explore more detailed models and experimental validation of the proposed design principles.
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 published 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.
More information: Ahmad A. Mannan et al, Design principles for engineering bacteria to maximise chemical production from batch cultures, Nature Communications (2025). DOI: 10.1038/s41467-024-55347-y
Citation: Systems engineering of cell factories almost doubles output, offering a sustainable fossil-fuel alternative (2025, January 21) retrieved 21 January 2025 from https://phys.org/news/2025-01-cell-factories-output-sustainable-fossil.html
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