Intelligent Microbial Heat Regulating Engine (IMHeRE) For Improving Thermotolerance Of Host And Efficiency Of Bioconversion

The growth and production of microorganisms in bioconversion are often hampered byheat stress. Therefore, developing new methods to improve the thermotolerance ofmicroorganisms for the fermentation industry, could significantly improve the productivity,shrink production costs, reduce energy consumption, increase substrate utilization, andmitigate the risk of contamination. In this study, an intelligent microbial heat regulatingengine (IMHeRE) was developed and customized for improving the thermo-robustness ofEscherichia coli, which integrated the thermotolerant system and quorum regulating system.At cell level, the thermotolerant system composed of different heat shock proteins(HSPs) and RNA thermometers (RNATs) could sensitively and hierarchically response heatchanging to expand the optimum temperature. Functional HSPs were mined fromextremophiles and introduced adaptively into targeted microbes. According to the behaviorsof engineered cells at different temperature, different well-done HSPs were rationallyassembled. RNATs were innovatively used to control the expression of HSPs for an economicsystem avoiding the waste of matter and energy. In addition, the RNATs made the wholesystem seamless and beforehand between two high temperatures to achieve the hierarchyheat resistance. Additionally, heat resistance is not only an individual behavior but also agroup behavior.At community level, the quorum regulating system could dynamically program thealtruistic individuals sacrifice to reduce the metabolic heat release via sensing the temperatureand cell density. The sensing temperature and cell density of quorum regulating system canbe regulated conveniently according to the need in practice. This was the first report ofartificial biological system sensitive to both temperature and cell density to program celldeath for improving the heat-resistance in community level.Through the hierarchical, dynamical and multilevel regulation, the strains withcustomized IMHeRE could obviously improve both the cell growth and production. In realapplication, the production of lysine was increased by5folds by IMHeRE at40°C. Our workshed new light on the development of the bioconversion by providing energy conservationand increasing the productivity.