“Metabolic burden” explained: stress symptoms and its related responses induced by (over)expression of (heterologous) proteins in Escherichia coli

Engineering bacterial strains to redirect the metabolism towards the production of a specific product has enabled the development of industrial biotechnology. However, rewiring the metabolism can have severe implications for a microorganism, rendering cells with stress symptoms such as a decreased growth rate, impaired protein synthesis, genetic instability and an aberrant cell size. On an industrial scale, this is reflected in processes that are not economically viable.

In literature, most stress symptoms are attributed to “metabolic burden”, however the actual triggers and stress mechanisms involved are poorly understood. Therefore, in this literature review, we aimed to get a better insight in how metabolic engineering affects Escherichia coli and link the observed stress symptoms to its cause. Understanding the possible implications that chosen engineering strategies have, will help to guide the reader towards optimising the envisioned process more efficiently.

This review addresses the gap in literature and discusses the triggers and effects of stress mechanisms that can be activated when (over)expressing (heterologous) proteins in Escherichia coli. It uncovers that the activation of the different stress mechanisms is complex and that many are interconnected. The reader is shown that care has to be taken when (over)expressing (heterologous) proteins as the cell’s metabolism is tightly regulated.