Design and engineering of photorespiratory bypasses in plants

Photorespiration is an essential metabolic process in C₃ plants, yet it imposes significant carbon losses of up to 30% or more. Synthetic biology has recently enabled the engineering of diverse photorespiratory bypasses to overcome this limitation. In this review, we categorize these bypasses into three major types based on glycolate carbon retention and CO₂ release. The first are chloroplast-localized carbon-releasing bypasses, which shift CO₂ release from mitochondria to chloroplasts, thereby establishing a localized CO₂-concentrating mechanism around Rubisco. The second are carbon-neutral bypasses, which conserve carbon during glycolate metabolism, thereby avoiding net carbon loss and often coupling bypasses with nitrogen assimilation. The third are carbon-positive bypasses, which not only minimize carbon loss but also achieve net carbon gain. We also emphasize some bypasses that redirect glycolate flow toward the production of more valuable metabolites, such as amino acids and organic acids. These strategies reveal that by reprogramming glycolate metabolism, it is possible to overcome the inherent photorespiratory limitations and increase photosynthetic efficiency in C₃ crops. Overall, this review offers an overview of current genetic strategies for suppressing photorespiration in model plants and crops and guides future optimization and rational design of photorespiratory bypasses.