Metabolic modeling links leaf anatomy to environment-specific benefits on the C3-C4 spectrum

C4 photosynthesis evolved from the ancestral C3 pathway through coordinated leaf anatomical and metabolic reorganization that concentrates CO2 to reduce photorespiration. Quantitative understanding of these structure-function relationships remains limited. Here we used anatomy-aware metabolic modeling of a mesophyll-bundle sheath cell system to analyze the interdependence between leaf anatomy and photosynthetic metabolism on the C3-C4 spectrum. Our model faithfully recapitulates the transitory steps from C3 to C4 photosynthesis, reveals a crucial role for plasmodesmata in enabling the C3 to C4 transition, and points at potential pre-C2 metabolic states that provide benefits under conditions that favor elevated photorespiration. Incorporating bundle cell suberisation with our model predicts reduction of PSII activity and dominance of the NADP-ME C4 subtype in leaves with suberized bundle sheath cells and proposes a role for oxygen evolution at PSII as a potential driver for this mechanism. Varying bundle sheath leakage and photorespiratory conditions along the C3-C4 spectrum identify conditions under which C3-C4 intermediate photosynthesis provides energetic benefits and underlines the notion of intermediate photosynthesis as a stable evolutionary state. Overall, our study sheds new light on the quantitative relationship between leaf anatomy and metabolism and its interaction with the environment and suggests targets for climate-adaptation in C3 plants.