l-lysine metabolism to N-hydroxypipecolic acid: an integral immune-activating pathway in plants

Plant J. 2018 Oct;96(1):5-21. doi: 10.1111/tpj.14037. Epub 2018 Sep 1.


l-lysine catabolic routes in plants include the saccharopine pathway to α-aminoadipate and decarboxylation of lysine to cadaverine. The current review will cover a third l-lysine metabolic pathway having a major role in plant systemic acquired resistance (SAR) to pathogen infection that was recently discovered in Arabidopsis thaliana. In this pathway, the aminotransferase AGD2-like defense response protein (ALD1) α-transaminates l-lysine and generates cyclic dehydropipecolic (DP) intermediates that are subsequently reduced to pipecolic acid (Pip) by the reductase SAR-deficient 4 (SARD4). l-pipecolic acid, which occurs ubiquitously in the plant kingdom, is further N-hydroxylated to the systemic acquired resistance (SAR)-activating metabolite N-hydroxypipecolic acid (NHP) by flavin-dependent monooxygenase1 (FMO1). N-hydroxypipecolic acid induces the expression of a set of major plant immune genes to enhance defense readiness, amplifies resistance responses, acts synergistically with the defense hormone salicylic acid, promotes the hypersensitive cell death response and primes plants for effective immune mobilization in cases of future pathogen challenge. This pathogen-inducible NHP biosynthetic pathway is activated at the transcriptional level and involves feedback amplification. Apart from FMO1, some cytochrome P450 monooxygenases involved in secondary metabolism catalyze N-hydroxylation reactions in plants. In specific taxa, pipecolic acid might also serve as a precursor in the biosynthesis of specialized natural products, leading to C-hydroxylated and otherwise modified piperidine derivatives, including indolizidine alkaloids. Finally, we show that NHP is glycosylated in Arabidopsis to form a hexose-conjugate, and then discuss open questions in Pip/NHP-related research.

Keywords: Arabidopsis thaliana; NHP; N-hydroxylation; N-hydroxypipecolic acid; N-oxygenation; flavin-containing monooxygenase; lysine metabolism; pipecolic acid; saccharopine pathway; systemic acquired resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arabidopsis / immunology
  • Arabidopsis / metabolism
  • Lysine / metabolism*
  • Metabolic Networks and Pathways
  • Pipecolic Acids / metabolism*
  • Plant Immunity*
  • Plants / immunology
  • Plants / metabolism


  • N-hydroxypipecolic acid
  • Pipecolic Acids
  • Lysine