System-level analysis of metabolic trade-offs during anaerobic photoheterotrophic growth inRhodopseudomonas palustris

Abstract

AbstractBackgroundLiving organisms need to allocate their limited resources in a manner that optimizes their overall fitness by simultaneously achieving several different biological objectives. Examination of these biological trade-offs can provide invaluable information regarding the biophysical and biochemical bases behind observed cellular phenotypes. A quantitative knowledge of a cell system’s critical objectives is also needed for engineering of cellular metabolism, where there is interest in mitigating the fitness costs that may result from human manipulation.ResultsTo study metabolism in photoheterotrophs, we developed and validated a genome-scale model of metabolism inRhodopseudomonas palustris, a metabolically versatile gram-negative purple non-sulfur bacterium capable of growing phototrophically on various carbons sources, including inorganic carbon and aromatic compounds. To quantitatively assess trade-offs among a set of important biological objectives during different metabolic growth modes, we used our new model to conduct an 8-dimensional multi-objective flux analysis of metabolism inR. palustris. Our results revealed that phototrophic metabolism inR. palustrisis a light-limited growth mode under anaerobic conditions, regardless of the available carbon source. Under photoheterotrophic conditions,R. Palustrisprioritizes the optimization of carbon efficiency, followed by ATP production and biomass production rate, in a Pareto-optimal manner. To achieve maximum carbon fixation, cells appear to divert limited energy resources away from growth and toward CO2fixation, even in presence of excess reduced carbon. We also found that to achieve the theoretical maximum rate of biomass production, anaerobic metabolism requires import of additional compounds (such as protons) to serve as electron acceptors. Finally, we found that production of hydrogen gas, of potential interest as a candidate biofuel, lowers the cellular growth rates under all circumstances.ConclusionsPhotoheterotrophic metabolism ofR. palustrisis primarily regulated by the amount of light it can absorb and not the availability of carbon. However, despite carbon’s secondary role as a regulating factor,R. palustris’metabolism strives for maximum carbon efficiency, even when this increased efficiency leads to slightly lower growth rates.