Abstract
Overflow metabolism is a phenomenon extended in nature, ranging from microbial to cancer cells. Accumulation of overflow metabolites pose a challenge for large-scale bioprocesses. Yet, the causes of overflow metabolism are not fully clarified. In this work, the underlying mechanisms, reasons and consequences of overflow metabolism in different organisms have been summarized. The reported effect of aerobic expression of Vitreoscilla haemoglobin (VHb) in different organisms are revised. The use of VHb to reduce overflow metabolism is proposed and studied through flux balance analysis in E. coli at a fixed maximum substrate and oxygen uptake rates. Simulations showed that the presence of VHb increases the growth rate, while decreasing acetate production, in line with the experimental measurements. Therefore, aerobic VHb expression is considered a potential tool to reduce overflow metabolism in cells.
Highlights
Overflow metabolism is a phenomenon extended in nature, ranging from microbial to cancer cells
A relatively straightforward explanation of overflow metabolism considers that a metabolic imbalance between catabolism and anabolism occurs at high glucose uptake rates [17]
Chen and Nielsen [33] modelled the energy metabolism of E. coli and S. cerevisiae coupled to proteomic analysis to successfully predict the start of overflow metabolism in relation to μ, qS, or ATP rate
Summary
Fast growing cells often display incomplete oxidation of the carbon source, even if oxygen is present in non-limiting amounts. The biotechnological production of molecules requires the transformation of a substrate (most commonly glucose) into the desired molecule Because these are autocatalytic processes, the amount of product that can be synthesized depends on the amount of cells in the culture. A standard procedure to maximize the amount of synthesized product is to attain an elevated amount of cells in the culture These so-called high cell-density cultures require elevated amounts of carbon source that lead to overflow metabolism. The accumulation of such by-products lowers the pH of the broth, affecting the cellular physiology.
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