Piperideine-6-carboxylic acid regulates vitamin B6 homeostasis and modulates systemic immunity in plants

Abstract

Dietary consumption of lysine in humans leads to the biosynthesis of Δ1-piperideine-6-carboxylic acid (P6C), with elevated levels linked to the neurological disorder epilepsy. Here we demonstrate that P6C biosynthesis is also a critical component of lysine catabolism in Arabidopsis thaliana. P6C regulates vitamin B6 homeostasis, and increased P6C levels deplete B6 vitamers, resulting in compromised plant immunity. We further establish a key role for pyridoxal and pyridoxal-5-phosphate biosynthesis in plant immunity. Our analysis indicates that P6C metabolism probably evolved through combining select lysine and proline metabolic enzymes horizontally acquired from diverse bacterial sources at different points during evolution. More generally, certain enzymes from the lysine and proline metabolic pathways were probably recruited in evolution as potential guardians of B6 vitamers and for semialdehyde detoxification. This study identifies the conversion of lysine to Δ1-piperideine-6-carboxylic acid (P6C) via pipecolate oxidase as a conserved pathway in plants and humans. P6C interacts with vitamin B6, affecting its homeostasis. Imbalances in vitamin B6 homeostasis disrupt defence in plants and cause neuropathology in humans.