Tyr‐Asp inhibition of glyceraldehyde 3‐phosphate dehydrogenase affects plant redox metabolism

How organisms integrate metabolism with the external environment is a central question in biology. Here, we describe a novel regulatory small molecule, a proteogenic dipeptide Tyr‐Asp, which improves plant tolerance to oxidative stress by directly interfering with glucose metabolism. Specifically, Tyr‐Asp inhibits the activity of a key glycolytic enzyme, glyceraldehyde 3‐phosphate dehydrogenase (GAPC), and redirects glucose toward pentose phosphate pathway (PPP) and NADPH production. In line with the metabolic data, Tyr‐Asp supplementation improved the growth performance of both Arabidopsis and tobacco seedlings subjected to oxidative stress conditions. Moreover, inhibition of Arabidopsis phosphoenolpyruvate carboxykinase (PEPCK) activity by a group of branched‐chain amino acid‐containing dipeptides, but not by Tyr‐Asp, points to a multisite regulation of glycolytic/gluconeogenic pathway by dipeptides. In summary, our results open the intriguing possibility that proteogenic dipeptides act as evolutionarily conserved small‐molecule regulators at the nexus of stress, protein degradation, and metabolism.