|
Project properties |
|
| Title | Application of pyruvate biosensor as a dynamic control valve to enhance biosynthesis in E. coli |
| Group | Systems and Synthetic Biology |
| Project type | thesis |
| Credits | 36 |
| Supervisor(s) | Zihan Gao, dr. Pieter Candry |
| Examiner(s) | Dr. Pieter Candry |
| Contact info | robert1.smith@wur.nl |
| Begin date | 2025/09/01 |
| End date | |
| Description | Natural products derived from bacterial metabolites contribute greatly to chemical, pharmaceutical, food, and agriculture industries, as well as environmental protection and other fields [1]. Pyruvate is a key metabolite that links glycolysis to the tricarboxylic acid (TCA) cycle, making it an important regulatory node for the central metabolism of the cell [2]. As pyruvate can be used to synthesize a variety of central metabolism-related chemicals, pyruvate biosensors could be an excellent tool to measure intracellular pyruvate levels enabling dynamic process control [3].
In this project, we aim to apply a pyruvate biosensor to increase product formation in Escherichia coli. The MS student will design genetic circuits and use PdhR-based biosensor as a valve to modulate the expression of key genes involved in cell growth and production formation. This dynamic control aims to achieve a balance between cell growth and product synthesis and enhance the yield of industrially relevant compounds. References 1. Choi, K. R., Jang, W. D., Yang, D., Cho, J. S., Park, D., & Lee, S. Y. (2019). Systems Metabolic Engineering Strategies: Integrating Systems and Synthetic Biology with Metabolic Engineering. Trends in biotechnology, 37(8), 817–837. https://doi.org/10.1016/j.tibtech.2019.01. 2. Anzai, T., Imamura, S., Ishihama, A., & Shimada, T. (2020). Expanded roles of pyruvate-sensing PdhR in transcription regulation of the Escherichia coli K-12 genome: fatty acid catabolism and cell motility. Microbial genomics, 6(10), mgen000442. https://doi.org/10.1099/mgen.0.000442. 3. Xu, X., Li, X., Liu, Y., Zhu, Y., Li, J., Du, G., Chen, J., Ledesma-Amaro, R., & Liu, L. (2020). Pyruvate-responsive genetic circuits for dynamic control of central metabolism. Nature chemical biology, 16(11), 1261–1268. https://doi.org/10.1038/s41589-020-0637-3 |
| Used skills | 1) Mastering molecular cloning techniques, including DNA extraction, PCR, plasmid construction and so on. |
| Requirements | 1) Prefer completed basic molecular microbiology & physiology course. 2) Basic lab skills. |