Original Research: Comparative constraint-based model development for thermophilic hydrogen production

A method for comparative constraint-based model development is presented; the constraint-based model for one organism is modified to create a model for a second organism based on synteny between the two annotated genome sequences. With this method a model was created for Thermotoga neapolitana, using the model for T. maritima as a template. Twenty-five of the 479 genes in the T. maritima model did not have orthologs in T. neapolitana, and the reactions associated with these genes were removed from the model. The T. neapolitana model was verified with flux balance analysis (FBA) and dynamic FBA. Sixteen carbon sources that supported FBA growth simulations for the T. maritima model did not support growth for the T. neapolitana model. Based on the simulations, glycerol and L-rhamnose were tested as T. neapolitana growth substrates, and experimental results confirmed the model prediction that these substrates are not metabolized by T. neapolitana. In addition to the generation of carbon source utilization hypotheses, cysteine and hydrogen metabolism hypotheses were also developed using the T. neapolitana model.