Optimizing ethanol production selectivity

Authors:
Raman Lall;Timothy J. Donohue;Simeone Marino;Julie C. Mitchell
Affiliations:
BACTER Institute, University of Wisconsin, Madison, WI 53706, United States;BACTER Institute, University of Wisconsin, Madison, WI 53706, United States and Department of Bacteriology and Great Lakes Bioenergy Center, University of Wisconsin, Madison, WI 53706, United Stat ...;Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, United States;BACTER Institute, University of Wisconsin, Madison, WI 53706, United States and Departments of Mathematics and Biochemistry, University of Wisconsin, Madison, WI 53706, United States
Venue:
Mathematical and Computer Modelling: An International Journal
Year:
2011

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Abstract

Lactococcus lactis metabolizes glucose homofermentatively to lactate. However, after disruption of the gene coding for lactate dehydrogenase, LDH, a key enzyme in NAD^+ regeneration, the glycolytic flux shifts from homolactic to mixed-acid fermentation with the redirection of pyruvate towards production of formate, acetate, ethanol and CO"2. A mathematical model of the pyruvate metabolism pathway that enhances ethanol production was developed from in vivo Nuclear Magnetic Resonance (NMR) time-series measurements that describe the dynamics of the metabolites in L. lactis. Both Michaelis-Menten and S-system models capture the observed in vivo dynamics of the glycolysis pathway in L. lactis, while prior models describe only the in vitro dynamics. The models provide insight into the maximization of selectivity of ethanol with respect to acetate and CO"2 as undesired products in multiple reactions. High concentrations of NADH and acetyl-CoA and low concentrations of pyruvate and NAD appear to maximize ethanol selectivity.