Biotechnological potential of respiring Zymomonas mobilis: A stoichiometric analysis of its central metabolism

The active, yet energetically inefficient electron transport chain of the ethanologenic bacterium Zymomonas mobilis could be used in metabolic engineering for redox-balancing purposes during synthesis of certain products. Although several reconstructions of Z. mobilis metabolism have been published, important aspects of redox balance and aerobic catabolism have not previously been considered. Here, annotated genome sequences and metabolic reconstructions have been combined with existing biochemical evidence to yield a medium-scale model of Z. mobilis central metabolism in the form of COBRA Toolbox model files for flux balance analysis (FBA). The stoichiometric analysis presented here suggests the feasibility of several metabolic engineering strategies for obtaining high-value products, such as glycerate, succinate, and glutamate that would use the electron transport chain to oxidize the excess NAD(P)H, generated during synthesis of these metabolites. Oxidation of the excess NAD(P)H would also be needed for synthesis of ethanol from glycerol. Maximum product yields and the byproduct spectra have been estimated for each product, with glucose, xylose, or glycerol as the carbon substrates. These novel pathways represent targets for future metabolic engineering, as they would exploit both the rapid Entner–Doudoroff glycolysis, and the energetically uncoupled electron transport of Z. mobilis.

► Central metabolism reconstruction is based on genome data and biochemical evidence.
► Use of Zymomonas mobilis uncoupled respiration for redox-balancing is suggested.
► A ready for simulations stoichiometric model of its central metabolism is presented.
► Stoichiometry of modified central metabolism generating excess NAD(P)H is analyzed.
► Metabolic engineering strategies for novel substrates and products are proposed.