Toward systems metabolic engineering in cyanobacteria: opportunities and bottlenecks.

We recently assessed the metabolism of Synechocystis sp PCC6803 through a constraints-based reconstruction and analysis approach and identified its main metabolic properties. These include reduced metabolic robustness, in contrast to a high photosynthetic robustness driving the optimal autotrophic metabolism. Here, we address how these metabolic features affect biotechnological capabilities of this bacterium. The search for growth-coupled overproducer strains revealed that the carbon flux re-routing, but not the electron flux, is significantly more challenging under autotrophic conditions than under mixo- or heterotrophic conditions. We also found that the blocking of the light-driven metabolism was required for carbon flux re-routing under mixotrophic conditions. Overall, our analysis, which represents the first systematic evaluation of the biotechnological capabilities of a photosynthetic organism, paradoxically suggests that the light-driven metabolism itself and its unique metabolic features are the main bottlenecks in harnessing the biotechnological potential of Synechocystis.