Design of thermo-responsive genetic controls with minimal heat-shock response
Haofeng Chen1, Shan Jiang1, Kaixuan Xu1, Ziyu Ding1, Jiangkai Wang1, Mingfeng Cao2,4*, Jifeng Yuan1,3*
1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian 361102, China
2 Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Key Laboratory for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen 361005, China.
3 Shenzhen Research Institute of Xiamen University, Shenzhen 518057, China
4 Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China
* Corresponding author Email: jfyuan@xmu.edu.cn and mfcao@xmu.edu.cn
ABSTRACT
As temperature serves as a versatile input signal, thermo-responsive genetic controls have gained of significant interest for recombinant protein production and metabolic engineering applications. The conventional thermo-responsive systems normally require the continuous exposure of heat stimuli to trigger the prolonged expression of targeted genes, and the accompanied heat-shock response is detrimental to the bioproduction process. In this study, we present the design of thermo-responsive quorum-sensing (ThermoQS) circuits to make Escherichia coli record transient heat stimuli. By converting the heat input into the accumulation of quorum-sensing molecules such as acyl-homoserine lactone derived from Pseudomonas aeruginosa, sustained gene expressions were achieved by a minimal heat stimulus. Moreover, we also demonstrated that reprogrammed the E. coli Lac operon to make it respond to heat stimuli with an impressive signal-to-noise ratio (S/N) of 15.3. Taken together, we envision that the ThermoQS systems reported in this study are expected to remarkably diminish both design and experimental expenditures for future metabolic engineering applications.
Key words: quorum-sensing; thermo-responsive circuit; Lac operon; heat-shock response; synthetic biology