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

How organisms integrate metabolism with the external environ-ment is a central question in biology. Here, we describe a novelregulatory small molecule, a proteogenic dipeptide Tyr-Asp, whichimproves plant tolerance to oxidative stress by directly interferingwith glucose metabolism. Specifically, Tyr-Asp inhibits the activityof a key glycolytic enzyme, glyceraldehyde 3-phosphate dehydro-genase (GAPC), and redirects glucose toward pentose phosphatepathway (PPP) and NADPH production. In line with the metabolicdata, Tyr-Asp supplementation improved the growth performanceof both Arabidopsis and tobacco seedlings subjected to oxidativestress conditions. Moreover, inhibition of Arabidopsis phospho-enolpyruvate carboxykinase (PEPCK) activity by a group ofbranched-chain amino acid-containing dipeptides, but not by Tyr-Asp, points to a multisite regulation of glycolytic/gluconeogenicpathway by dipeptides. In summary, our results open the intrigu-ing possibility that proteogenic dipeptides act as evolutionarilyconserved small-molecule regulators at the nexus of stress, proteindegradation, and metabolism.