Synthesis of β-Alanine From Isoleucine and Propionate Catabolism via Aminotransferases

In plants, the nonproteinogenic amino acid β-alanine plays a role in response to hypoxia, flooding, drought, heat, and heavy metal stress conditions. It is also a key intermediate in the synthesis of essential molecules including vitamin B5 and coenzyme A (CoA) through the condensation reaction with pantoate. While the syntheses of pantoate, vitamin B5, and CoA appear to be conserved across plants and bacteria, the synthesis of β-alanine is not. Bacteria and fungi use aspartate, whereas plants can use uracil, spermidine, or propionate to synthesize β-alanine. Given that these three precursors can be formed from the metabolism of glutamine, arginine, isoleucine, and valine, the synthesis of β-alanine could be linked to numerous pathways. Studies of valine catabolism in Arabidopsis suggested that some branched-chain amino acids could in fact serve as precursors for the synthesis of β-alanine. Using GC-MS and isotopically labeled isoleucine and propionate, we linked their metabolism to the synthesis of β-alanine via a proposed transamination of malonate semialdehyde. We then identified three aminotransferases that each catalyzed this final reversible transamination reaction. These results affirm our hypothesis that isoleucine metabolism is also linked to the synthesis of β-alanine via the transamination of metabolic intermediates.