Trade-Offs in Biosensor Optimization for Dynamic Pathway Engineering
| Autor: | Diego A. Oyarzún, Babita K. Verma, Ahmad A. Mannan, Fuzhong Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
Computer science Biomedical Engineering model-based design Biosensing Techniques Multi-objective optimization 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Bottleneck Metabolic engineering Synthetic biology 03 medical and health sciences Robustness (computer science) 010608 biotechnology Escherichia coli biosensor optimization pathway optimization Promoter Regions Genetic 030304 developmental biology 0303 health sciences dynamic pathway control General Medicine metabolite biosensor Metabolic Engineering Synthetic Biology Biochemical engineering metabolic engineering Host (network) Flux (metabolism) Biosensor |
| Zdroj: | Verma, B, Mannan, A, Zhang, F & Oyarzún, D A 2022, ' Trade-offs in biosensor optimization for dynamic pathway engineering ', ACS Synthetic Biology, vol. 11, no. 1, pp. 228-240 . https://doi.org/10.1021/acssynbio.1c00391 |
| ISSN: | 2161-5063 |
| DOI: | 10.1021/acssynbio.1c00391 |
| Popis: | Recent progress in synthetic biology allows the construction of dynamic control circuits for metabolic engineering. This technology promises to overcome many challenges encountered in traditional pathway engineering, thanks to their ability to self-regulate gene expression in response to bioreactor perturbations. The central components in these control circuits are metabolite biosensors that read out pathway signals and actuate enzyme expression. However, the construction of metabolite biosensors is a major bottleneck for strain design, and a key challenge is to understand the relation between biosensor dose-response curves and pathway performance. Here we employ multiobjective optimization to quantify performance trade-offs that arise in the design and calibration of metabolite biosensors. Our approach reveals strategies for tuning dose-response curves along an optimal trade-off between production flux and the cost of an increased expression burden on the host. We explore properties of control architectures built in the literature, and identify their advantages and caveats in terms of performance and robustness to growth conditions and leaky promoters. We demonstrate the optimality of a control circuit for glucaric acid production in Escherichia coli, which has been shown to increase titer by 2.5-fold as compared to static designs. Our results lay the groundwork for the automated design of control circuits for pathway engineering, with applications in the food, energy and pharmaceutical sectors. |
| Databáze: | OpenAIRE |
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