S120: Application of metabolic flux modeling to optimize metabolite production by the acetogen Moorella thermoacetica when grown on hydrogen gas or direct current

The use of microorganisms to produce value-added products dates back to the earliest days of civilization. Examples include beer production by the Mesopotamians, cheese making in ancient Egypt, and the bioleaching of metals by the Phoenicians. However, economic incentives to expand and improve such processes necessitate a better understanding of microbial metabolisms.  One method to predict the flow of energy and material through microbial systems is metabolic stoichiometric modeling, which extracts systemic information from molecular-level network structure and conservation relationships.  

To date, such a model has been constructed from the annotated genome of the acetogen, Moorella thermoacetica, and the output data have been sorted against various cellular strategies, including maximal efficiency of biomass yield per substrate, and substrate consumption in the presence of high exogenous concentrations.  Output from such models has successfully predicted substrate concentrations that maximize ethanol production, as opposed to acetate, when M. thermoacetica was grown on CO₂ and H₂.  In fact, the molar ratio of produced ethanol:acetate increased 80-fold when substrate conditions were adjusted per the models predictions.  Under other substrate conditions, including H₂ and nitrogen limited growth; we were able to predict substrate consumption, biomass production, and metabolite production to within 5 and 10 percent error.  In addition, M. thermoacetica was grown using direct current as the sole electron donor, and as with H₂ supported growth, we observed an apparent functionality between the electron donor/acceptor availability and metabolite production.