Rubisco limits plant breeding: can biodiversity unlock it?

Photosynthesis has been underestimated as a breeding target. A workflow that identifies or engineers superior Rubisco variants and introduces them into crops is urgently needed. Photosynthesis is the foundation of life on Earth, yet it remains inefficient in crop plants. At the heart of this lies Rubisco, the most abundant enzyme on Earth and the primary bottleneck in carbon fixation. Despite its central role in determining photosynthetic capacity and crop yield, efforts to improve it have been constrained by three persistent blind spots: an overreliance on model species, inadequate screening platforms, and the challenge of chloroplast transformation. This perspective argues that closing these gaps requires an integrated framework connecting structural biology, natural biodiversity, and synthetic approaches. Molecular dynamics simulations informed by high-resolution crystal structures offer a powerful entry point for identifying residues with the greatest predicted impact on CO₂/O₂ specificity and carboxylation turnover. These insights should then guide two complementary discovery strategies: directed engineering of novel substitutions, and biodiversity screening of plants adapted to extreme environments, where sustained selective pressure has shaped Rubisco variants absent in domesticated crops. Once promising variants are identified through either approach, they must be screened and validated in a biologically meaningful platform; cyanobacteria are emerging as a strong candidate, coupling Rubisco activity directly to growth under light-dark cycles in ways that E. coli, the current model for directed evolution, cannot replicate. Ultimately, without a robust method for modifying the chloroplast genome in crop species, even the most catalytically superior variant will remain confined to the laboratory. This framework advances Rubisco improvement from isolated engineering efforts toward a coherent path for developing photosynthetically-superior-crops with enhanced yields under a changing climate.