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A first generation genetically modified strain of Corynebacterium glutamicum has been assessed for its potential to synthesise and accumulate the vitamin pantothenic acid in the medium using fed-batch cultivation technology, with biomass concentration controlled by isoleucine limitation. Kinetic analysis of specific rates throughout the process has been used to model carbon flux through both central metabolism and the specific pathways involved in product formation. Flux towards pantothenic acid is potentially high but much of this flux is dissipated as by-products within associated pathways, notably linked to amino acid synthesis. The major limitation of vitamin production in this strain is linked to the tenfold higher flux of keto-isovalerate towards valine rather than pantothenic acid. Attempts to modify this ratio by imposing nitrogen limitation provoked carbon overflow as unidentified non-nitrogenous compounds. The observed accumulation of glycine suggests that the flux towards pantothenate production may by limited by the rate of the pathway intermediate (5,10-methylene-tetrahydrofolate) regeneration.

Cell growth in a chemostat is a well-documented research topic. How cells uptake the available substrate to gain weight and engage cell division is not generally taken into account in the modelling bioreactors. In fact, the growth rate is related to a population doubling time whereas the microorganisms’ growth in mass is due to the mass transfer of substrates from the liquid phase to the biotic phase. Clearly, growth in mass precedes growth in number. Similarly, the transport of substrates down to the cell scale precedes the mass transfer. This article's main feature is a two-dimensional population balance model that allows to uncouple growth in mass and growth in number when the equilibrium between a cell population and its environment is disrupted. The cell length and the rate of anabolism are chosen as internal variables. It is proved that the hypothesis “growth in number = growth in mass” is valid at steady-state or in exponential growth only. The glucose uptake is assumed driven by two transport systems with a different affinity constant for the substrate. This combination of two regulated uptake systems operating in parallel explains a 3-fold increase in the uptake following a glucose pulse, but can also predict substrate uptake rates higher than the maximal batch value as observed in some experiments. These features are obtained by considering carbon fluxes in the formulation of regulation principles for uptake dynamics. The population balance's implementation in a multi-compartment reactor is a natural prospective work and allows extensions to industrial processes. [ABSTRACT FROM AUTHOR]