Flavin Monooxygenase-Generated N-Hydroxypipecolic Acid Is a Critical Element of Plant Systemic Immunity

Abstract

Following a previous microbial inoculation, plants can induce broad-spectrum immunity to pathogen infection, a phenomenon known as systemic acquired resistance (SAR). SAR establishment in Arabidopsis thaliana is regulated by the Lys catabolite pipecolic acid (Pip) and flavin-dependent-monooxygenase1 (FMO1). Here, we show that elevated Pip is sufficient to induce an FMO1-dependent transcriptional reprogramming of leaves that is reminiscent of SAR. In planta and in vitro analyses demonstrate that FMO1 functions as a pipecolate N-hydroxylase, catalyzing the biochemical conversion of Pip to N-hydroxypipecolic acid (NHP). NHP systemically accumulates in plants after microbial attack. When exogenously applied, it overrides the defect of NHP-deficient fmo1 in acquired resistance and acts as a potent inducer of plant immunity to bacterial and oomycete infection. Our work has identified a pathogen-inducible L-Lys catabolic pathway in plants that generates the N-hydroxylated amino acid NHP as a critical regulator of systemic acquired resistance to pathogen infection.

Calcium‐dependent protein kinase 5 links calcium signaling with N‐hydroxy‐l‐pipecolic acid‐ and SARD1‐dependent immune memory in systemic acquired resistance

“…Instead, inoculated plants showed increased susceptibility, like unprimed Col‐0, or became even more susceptible ( fmo1 × CPK5‐YFP#7 ). These data are consistent with the FMO1 enzyme catalyzing the synthesis of the SAR‐inducing metabolite NHP from the precursor Pip (Hartmann et al ., ).…”

The Arabidopsis thaliana N‐recognin E3 ligase PROTEOLYSIS1 influences the immune response

“…Increased SARD4 protein levels in prt1‐1 were not accompanied by changed SARD4 transcript accumulation, nor by accumulation of AGD2‐like defense response protein1 ( ALD1 ), the other enzyme involved in Pip biosynthesis from L‐lysine (Hartmann et al, ) (Figure c), which may indicate that they are subject to post‐translational regulation. Recently, it was demonstrated that Pip biosynthesis is tightly regulated by EDS1/PAD4 signaling (Hartmann & Zeier, ; Hartmann et al, ). Increased abundance of EDS1 (and several EDS1‐responsive proteins) in untreated prt1‐1 plants was accompanied by small changes in the accumulation of EDS1‐responsive transcripts, including FLAVIN‐DEPENDENT MONOOXYGENASE 1 ( FMO1 ), a key component of plant immunity (Bartsch et al, 2006; Koch et al, 2006; Mishina and Zeier, 2006) that catalyzes the hydroxylation of Pip, CALMODULIN‐BINDING PROTEIN 60‐LIKEg ( CBP60g ) and ISOCHORISMATE SYNTHASE1 ( ICS1 ) (Cui et al, ) (Figure c).…”

JMJ14 encoded H3K4 demethylase modulates immune responses by regulating defence gene expression and pipecolic acid levels

“…Unlike jmj14 , exogenous Pip was able to fully restore SAR in ald1 plants (Navarova et al , ; C. Wang et al , ), which suggests that Pip deficiency alone might not account for SAR defect in jmj14 plants. Considering JMJ14 also regulated FMO1 expression, which acts downstream of Pip (Chen et al , ; Hartmann et al , ), lends to the possibility that a SAR defect in jmj14 may be associated with both Pip and its downstream signal NHP. However, considering jmj14 only shows attenuated expression of FMO1 , exogenous Pip should have compensated for any reduction in NHP levels and restored SAR in jmj14 plants.…”

“…The sard4 plants has been reported to show normal (Hartmann et al , ) or compromised SAR (Ding et al , ) and the reason for this variable SAR phenotype is not clear. Pip is hydroxylated to N‐hydroxy‐pipecolic acid (NHP) by FLAVIN‐DEPENDENT MONOOXYGENASE 1 (FMO1) and FMO1 is essential for biologically induced SAR (Mishina & Zeier, ; Chen et al , ; Hartmann et al , ). NHP confers SAR on both ald1 and fmo1 plants (Chen et al , ; Hartmann et al , ), suggesting that NHP acts downstream of Pip (Hartmann & Zeier, ).…”

“…Pip is hydroxylated to N‐hydroxy‐pipecolic acid (NHP) by FLAVIN‐DEPENDENT MONOOXYGENASE 1 (FMO1) and FMO1 is essential for biologically induced SAR (Mishina & Zeier, ; Chen et al , ; Hartmann et al , ). NHP confers SAR on both ald1 and fmo1 plants (Chen et al , ; Hartmann et al , ), suggesting that NHP acts downstream of Pip (Hartmann & Zeier, ). Relationship between NHP and other SAR inducers remains unknown at present.…”