AUTHOR=Carteni Fabrizio , Occhicone Alessio , Giannino Francesco , Vincenot Christian E. , de Alteriis Elisabetta , Palomba Emanuela , Mazzoleni Stefano 

TITLE=A General Process-Based Model for Describing the Metabolic Shift in Microbial Cell Cultures

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.521368

DOI=10.3389/fmicb.2020.521368

ISSN=1664-302X

ABSTRACT=<p>The metabolic shift between respiration and fermentation at high glucose concentration is a widespread phenomenon in microbial world, and it is relevant for the biotechnological exploitation of microbial cell factories, affecting the achievement of high-cell-densities in bioreactors. Starting from a model already developed for the yeast <italic>Saccharomyces cerevisiae</italic>, based on the System Dynamics approach, a general process-based model for two prokaryotic species of biotechnological interest, such as <italic>Escherichia coli</italic> and <italic>Bacillus subtilis</italic>, is proposed. The model is based on the main assumption that glycolytic intermediates act as central catabolic hub regulating the shift between respiratory and fermentative pathways. Furthermore, the description of a mixed fermentation with secondary by-products, characteristic of bacterial metabolism, is explicitly considered. The model also represents the inhibitory effect on growth and metabolism of self-produced toxic compounds relevant in assessing the late phases of high-cell density culture. Model simulations reproduced data from experiments reported in the literature with different strains of non-recombinant and recombinant <italic>E. coli</italic> and <italic>B. subtilis</italic> cultured in both batch and fed-batch reactors. The proposed model, based on simple biological assumptions, is able to describe the main dynamics of two microbial species of relevant biotechnological interest. It demonstrates that a reductionist System Dynamics approach to formulate simplified macro-kinetic models can provide a robust representation of cell growth and accumulation in the medium of fermentation by-products.</p>