CO2 - Intrinsic Product, Essential Substrate, and Regulatory Trigger of Microbial and Mammalian Production Processes.

Bastian Blombach,Ralf Takors

doi:10.3389/fbioe.2015.00108

Bastian Blombach, Ralf Takors

Open Access

https://doi.org/10.3389/fbioe.2015.00108

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Abstract

Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence, dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. At the same time, CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular depend on cellular activities and physical constraints such as hydrostatic pressures, aeration, and the efficiency of mixing in large-scale bioreactors. Besides, local levels might also act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity, and transcriptional regulation.

Highlights

One of the most decisive decisions which needs to be made when developing novel bioprocesses is whether the final process will run under anaerobic or aerobic conditions
While therapeutic proteins and fine chemicals are typically produced in bioreactor of 5–20 m3 scale, the production of commodities is usually performed in 50–500 m3 size – or even larger
Metabolism of all living organisms is equipped with a set of carboxylases incorporating CO2 or bicarbonate (HCO3− ) into organic molecules and decarboxylases releasing CO2 in the environment

Summary

Bastian Blombach and Ralf Takors*

Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. Anaplerotic reactions make use of the abundant CO2 / HCO3− levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular CO2 / HCO3− depend on cellular activities and physical constraints such as hydrostatic pressures, aeration, and the efficiency of mixing in large-scale bioreactors. Local CO2 / HCO3− levels might act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of CO2 / HCO3− in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity, and transcriptional regulation

Introduction

Metabolic Release and Incorporation

Findings

Conclusion