Engineered autonomous dynamic regulation of metabolic flux

Metabolic engineering is a powerful tool to reprogramme cells to produce value-added chemicals. Such engineering strategies require the fine-tuning of a cell’s metabolism to balance competition for resources and prevent negative impacts on growth. Dynamic regulation enables the shifting of resources or metabolic flux toward different pathways based on a received input to increase titres of value-added chemicals in microbial production strains. In this Review, we discuss autonomous dynamic regulation, that is, responses triggered directly by a stimulus without the need for human intervention, and its application to metabolic engineering. We highlight strategies to control the transcription of genes using metabolite-specific regulation, including by transcription factors and through biosensing, and non-specific regulation, in particular, environmental regulation, growth-phase responses and quorum sensing, examining the application of these regulation strategies to the bioproduction of different chemicals.