A synthetic ecosystem for the multi-level modelling of heterotroph-phototroph metabolic interactions

Marine ecosystems are characterized by an intricate set of interactions. One of the most important occurs through the exchange of dissolved organic matter (DOM) provided by phototrophs and used by heterotrophic bacteria as their main carbon and energy source. This metabolic interaction represents the foundation of the entire ocean food-web. Here we have assembled a synthetic ecosystem to assist the systems-level investigation of this biological association. This was achieved by building an integrated, genome-scale metabolic reconstruction using two model organisms (a diatom Phaeodactylum tricornutum and an heterotrophic bacterium, Pseudoalteromonas haloplanktis). The model was initially analysed using a constraint-based approach (Flux Balance Analysis, FBA) and then turned into a dynamic (dFBA) model to simulate a diatom-bacteria co-culture and to study the effect of changes in growth parameters on such a system. Furthermore, we developed a simpler dynamic Ordinary Differential Equations (ODEs) system that, fed with dFBA results, was able to qualitatively describe this synthetic ecosystem and allowed performing stochastic simulations to assess the effect of noise on the overall balance of this co-culture. We show that our model represents known metabolic cross-talks of a phototroph-heterotroph system, including mutualism and competition for inorganic ions (i.e., phosphate and sulphate). In addition, the dynamic simulation predicts realistic growth rates for both the diatom and the bacterium and a steady-state balance between diatom and bacterial cell concentration that matches those determined in experimental co-cultures. This steady state, however, is reached following an oscillatory trend, a behaviour that is typically observed in the presence of metabolic co-dependencies. Finally, we show that, at high diatom/bacteria cell concentration ratio, stochastic fluctuations can lead to the extinction of bacteria from the co-culture, causing an explosion of diatom population. We anticipate that the developed synthetic ecosystem will serve as a basis for the generation of testable hypotheses and as a scaffold for integrating and interpreting -omics data from experimental co-cultures.