Metabolic flux analysis

In algae carbon dioxide and inorganic compounds like nitrate and phosphate are converted into biomass and different types of products like, for example, lipids. Light is used as energy source. This is done through a complex set of biochemical reactions that take place in different compartments with the most relevant being  the chloroplast, mitochondria and the cytosol. To obtain more insight in metabolism metabolic flux balancing is a useful tool.
Using the known stoichiometry of the biochemical reactions a metabolic network model can be constructed (Figure 1). Next, by assuming steady state and constructing mass balances over the intracellular metabolites the rates with which these biochemical reactions take place (the fluxes) can be connected to the consumption of substrates and production of biomass and other compounds like lipids. These network models can be used essentially in two ways:

  1. One is that by measuring the rates with which substrates are consumed and biomass and products are formed, the intracellular flux distribution can be calculated. Next metabolic flux distributions under different conditions can be compared. For example, the flux distribution under conditions where no lipids are produced can be compared with the flux distribution under conditions where more or less lipid formation occurs. This can give insight in possible metabolic bottlenecks. Especially, in combination with measurement of gene expression this technique can give insight into regulation mechanisms.
  2. The second option is to use these models to calculate optimal solutions using linear optimization techniques. For example, one can calculate the flux distribution resulting in optimal biomass growth or product formation. This gives insight in why algae have a certain metabolic flux distribution. In addition, metabolic reactions can be added to the network or deleted from the network and the effect on biomass and product formation can be studied in silico. In this way these models can help improving, for example, product formation by either engineering the conditions in the environment of the algae or by genetic engineering.

Example of a simplified metabolic network model for Algae:



 

  
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