Society for Mathematical Biology nautilus logo

International Conference on Mathematical Biology and

Annual Meeting of The Society for Mathematical Biology,

July 27-30, 2009

University of British Columbia, Vancouver

.

Program

MSD5c
John Morgan
Purdue University
Title In silico prediction and experimental measurements of metabolic fluxes in photosynthetic organisms
Abstract Photoautotrohpic metabolism involves the utilization of light energy to fix available CO2 into complex organic molecules. A major goal of our research is to have a systems level understanding of metabolism that will enable the rational design of production of valuable metabolites from photosynthetic systems. To accomplish this goal, a key tool is the measurement of metabolic fluxes. The first task is to reconstruct the metabolic network for the organism of interest. We have done this for a model prokaryote, Synechocystis PCC6803, and a genome scale model for photosynthetic eukaryotic algae, Chalmydomonas reinhardtii. Predictions of metabolic fluxes are accomplished by specifying an objective function, such as maximize biomass synthesis, and performing linear programming to determine optimal fluxes satisfying stoichiometric constraints. We will present our findings for metabolic flux distributions under hetero-, mixo-, and autotrophic growth conditions.
Metabolic flux analysis is widely used for quantification of phenotypes under varying environmental and genetic conditions. However, inherent limitations have prevented the application of steady state 13C-MFA to purely autotrophic metabolism, wherein CO2 is the sole carbon source. This is due to the fact that, in autotrophic systems under conditions of isotopic steady state, every single carbon atom in every downstream molecule has the same labeling percentage as the single input carbon (CO2), irrespective of flux distribution. However, the pattern of change in isotopic label distribution as the steady state is attained does depend on the fluxes. This type of labeling information is utilized in recently developed techniques of instationary 13C-MFA, which enable measurement of fluxes at a metabolic steady state, while following changes in 13C labeling patterns of metabolic intermediates as a function of time, in response to a step change in 13C label input. In this work, we utilize the instationary 13C- MFA technique with the elementary metabolite unit (EMU) formulation to measure central carbon fluxes under photoautotrophic conditions for the first time. We will compare in silico and experimental results for the cyanobacterium, Synechocystis sp. PCC 6803.
LocationWoodward 5