Extended Data Fig. 1: A simplified model illustrating lysine catabolic pathway.

(a) In the saccharopine pathway, lysine is first converted to saccharopine by lysine ketoglutarate reductase (LKR), which is then converted to glutamate and AASA by saccharopine dehydrogenase (SDH). AASA can spontaneously convert to P6C, thus joining the Pip-pathway. AASA is metabolized to AAA by aldehyde dehydrogenase (AASAdh/Antiquitin) encoded by the ALDH7B4 gene in Arabidopsis. (b) Lysine undergoes oxidative deamination to form ε-amino-α-caproric acid, followed by cyclization to piperideine-2 carboxylic acid (P2C) and subsequent reduction to pipecolic acid (Pip). Lysine to P2C and P2C to Pip steps are catalyzed by ALD1 and SARD4, respectively. Pip is also oxidized to piperideine-2 carboxylic acid (P6C) by SOX (PipOX) or to N-hydroxypipecolic acid (NHP) via the FMO1 flavin monooxygenase. Low level accumulation of Pip in sard4 plants suggest involvement of additional unknown enzymes (indicated by?). Enzymes are shown in green.