title: Toward systems metabolic engineering in cyanobacteria: opportunities and bottlenecks.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Nogales
authors.forename: Steinn
authors.initials: S
authors.lastname: Gudmundsson
authors.forename: Ines
authors.initials: I
authors.lastname: Thiele
mesh_terms: D010788:Photosynthesis; D046939:Synechocystis / Q000502:physiology*; D049490:Systems Biology
keywords: COBRA methods; Synechocystissp. PCC6803; biosustainability; genome-scale modeling; metabolic engineering; photosynthetic robustness