Toward a systems metabolic engineering approach to improve thermotolerance of Escherichia coli

Escherichia coli is one of the leading microbial chassis for bioproduct manufacturing in biotechnology. However, its use in high-temperature bioprocesses is restricted to its mesophilic nature. Rational engineering for improving thermotolerance in E. coli is challenging due to the limited understanding of the molecular functions and interactions involved in supraoptimal thermal adaptation. In recent decades, various approaches have been applied to increase the thermotolerance of E. coli. In this review, we examine the effect of temperature on cellular growth and thermal adaptation at supraoptimal temperatures and discuss how this knowledge can be applied to increase thermotolerance in E. coli. We particularly emphasize systems, synthetic, and evolutionary biology approaches that translate into systems metabolic engineering strategies to improve E. coli thermotolerance. We expect that systems-level insights into heat-stress physiology will enable data-driven strategies for the development of thermotolerant E. coli strains that can be used in high-temperature bioprocesses.