Kinetic models of catabolism in LAB

Title: Kinetic models of catabolism in LAB

Description

In the analysis of large genome-scale metabolic models, it is often assumed that the network is optimized towards some objective function (Price, Reed et al. 2004) . This is in most cases biomass formation, i.e. yield. With such an objective function, it is assumed that metabolism is as efficient as possible. However, lactic acid bacteria are adapted to very rich environments where efficiency is not important. Hence, predictions of metabolic fluxes and biomass yields fail under the assumption of optimal, efficient, biomass formation. Growth rate or maybe simply catabolic rate (consuming substrates as fast as possible, spoiling it for everybody else) is a more likely strategy (Pfeiffer, Schuster et al. 2001; Pfeiffer and Schuster 2005) .

Where yields can be predicted with purely stoichiometric models, predictions of rates need information on enzyme kinetics. Fortunately, as a first step we only need to model catabolism, which is relatively small (some 20 enzymes), whereas anabolism is huge (>400 reactions). The idea would be to calculate fluxes specifically in the kinetic model, and use these fluxes as constraints in the stoichiometric model. Lactic acid bacteria are an interesting case for such a combination of stoichiometric models with kinetic models, since catabolism is almost completely separated from anabolism. Kinetic models of parts of catabolism do exist, and can be used as a starting point. A genome-scale model of Lactobacillus plantarum is available, and one for Lactococcus lactis in under way. This project would aim at:

•  Evaluating and improving existing kinetic models of catabolism in LAB

•  applying the outcome of the kinetic model as constraint in the genome-scale model

Supervisor:

Bas Teusink

Daily supervision:

Richard Notebaart, Christof Francke

References:

Pfeiffer, T. and S. Schuster (2005). "Game-theoretical approaches to studying the evolution of biochemical systems." Trends Biochem Sci 30 (1): 20-5.

Pfeiffer, T., S. Schuster, et al. (2001). "Cooperation and competition in the evolution of ATP-producing pathways." Science 292 (5516): 504-7.

Price, N. D., J. L. Reed, et al. (2004). "Genome-scale models of microbial cells: evaluating the consequences of constraints." Nat Rev Microbiol 2 (11): 886-97.