News about amino acid metabolism in plant–microbe interactions

Engaging with beneficial microbes while fending off pathogenic ones is crucial for plant health and crop yield.Recent findings show that amino acid metabolism is closely linked to plant–microbe interactions, providing signaling molecules, nutrients, and defense compounds.Great progress has been made in the field of amino-acid-derived secondary metabolites and signaling molecules, leading to the identification of biochemical synthesis pathways, transport, and inactivation mechanisms.Insight into the mechanisms of amino acid sensing and signaling will be critical to unraveling plant–microbe communication. Plants constantly come into contact with a diverse mix of pathogenic and beneficial microbes. The ability to distinguish between them and to respond appropriately is essential for plant health. Here we review recent progress in understanding the role of amino acid sensing, signaling, transport, and metabolism during plant–microbe interactions. Biochemical pathways converting individual amino acids into active compounds have recently been elucidated, and comprehensive large-scale approaches have brought amino acid sensors and transporters into focus. These findings show that plant central amino acid metabolism is closely interwoven with stress signaling and defense responses at various levels. The individual biochemical mechanisms and the interconnections between the different processes are just beginning to emerge and might serve as a foundation for new plant protection strategies. Plants constantly come into contact with a diverse mix of pathogenic and beneficial microbes. The ability to distinguish between them and to respond appropriately is essential for plant health. Here we review recent progress in understanding the role of amino acid sensing, signaling, transport, and metabolism during plant–microbe interactions. Biochemical pathways converting individual amino acids into active compounds have recently been elucidated, and comprehensive large-scale approaches have brought amino acid sensors and transporters into focus. These findings show that plant central amino acid metabolism is closely interwoven with stress signaling and defense responses at various levels. The individual biochemical mechanisms and the interconnections between the different processes are just beginning to emerge and might serve as a foundation for new plant protection strategies. In a natural environment outside controlled laboratory conditions, plants interact with complex microbial communities. Microbes usually benefit from the rich supply of organic compounds (including amino acids) in the vicinity of a plant. Some might manipulate plant metabolism to access nutrients, either in return for some kind of service during mutualistic interactions or without benefit for the plant in commensals, whereas pathogens even cause damage to the plant (Figure 1). In any case, microbes need to evade or suppress immune reactions and the plant needs to discriminate between potentially harmful and beneficial interactions to react accordingly. The plant's set of measures may include withdrawing nutrients to starve pathogens (e.g., [1.Mur L.A.J. et al.Moving nitrogen to the centre of plant defence against pathogens.Ann. Bot. 2017; 119: 703-709PubMed Google Scholar]) or supplying a specific set of compounds to establish beneficial interactions (e.g., [2.Lanfranco L. et al.Partner communication and role of nutrients in the arbuscular mycorrhizal symbiosis.New Phytol. 2018; 220: 1031-1046Crossref PubMed Scopus (124) Google Scholar]). In the case of a pathogen attack, plants also have to activate appropriate defense responses and to alert nonaffected parts of the plant about impending danger to restrict pathogen growth [3.Zhou J.-M. Zhang Y. Plant immunity: danger perception and signaling.Cell. 2020; 181: 978-989Abstract Full Text Full Text PDF PubMed Scopus (366) Google Scholar]. In this review we discuss how plant amino acid metabolism is involved in shaping these different interactions between plants and microbes. Recent studies have shed light on interspecies communication during first contact, and have demonstrated how plants use amino acids to produce specialized metabolites (see Glossary) as a means to selectively promote proliferation of beneficial microbes. Amino acid transport is required for nutrient exchange and, in combination with specific receptors, might be involved in amino acid sensing and signaling mechanisms during interaction with microbes. Amino acid metabolism is also crucial for immune signaling within the plant during the establishment of a systemic immune reaction. The aromatic amino acids Tyr, Phe, and Trp are synthesized in plastids and also in the cytosol by the shikimate pathway [4.Lynch J.H. Dudareva N. Aromatic amino acids: a complex network ripe for future exploration.Trends Plant Sci. 2020; 25: 670-681Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar]. In addition to being incorporated into proteins, they serve as precursors for a diverse set of specialized metabolites (Figure 2) [5.Yokoyama R. et al.The entry reaction of the plant shikimate pathway is subjected to highly complex metabolite-mediated regulation.Plant Cell. 2021; 33: 671-696Crossref PubMed Scopus (39) Google Scholar]. A considerable share of carbon flow (≥30%) is directed through the shikimate pathway to produce pigments, defense compounds, and the cell-wall component lignin [6.Maeda H. Dudareva N. The shikimate pathway and aromatic amino acid biosynthesis in plants.Annu. Rev. Plant Bio. 2012; 63: 73-105Crossref PubMed Scopus (875) Google Scholar]. Plant specialized metabolites can act as nutrient sources, signaling molecules, or toxins for individual microbial strains, thereby shaping the overall composition of the microbiome [7.Jacoby R.P. et al.Recent advances in the role of plant metabolites in shaping the root microbiome.F1000Research. 2020; 9PMC7047909Crossref PubMed Scopus (43) Google Scholar,8.Pascale A. et al.Modulation of the root microbiome by plant molecules: the basis for targeted disease suppression and plant growth promotion.Front. Plant Sci. 2020; 10: 1741Crossref PubMed Scopus (276) Google Scholar]. Recently there has been some significant progress in understanding both the regulation of aromatic amino acid metabolism and the role of individual aromatic phytochemicals in coordinating plant–microbe interactions. The synthesis rates for the individual aromatic amino acids are regulated by product inhibition of the respective committed step, which is a common scheme in amino acid synthesis in plants [4.Lynch J.H. Dudareva N. Aromatic amino acids: a complex network ripe for future exploration.Trends Plant Sci. 2020; 25: 670-681Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar,6.Maeda H. Dudareva N. The shikimate pathway and aromatic amino acid biosynthesis in plants.Annu. Rev. Plant Bio. 2012; 63: 73-105Crossref PubMed Scopus (875) Google Scholar]. However, in addition, the entry reaction of the shikimate pathway – catalyzed by 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DHS) – is controlled via a complex pattern of allosteric feedback inhibition in a tissue-specific manner [5.Yokoyama R. et al.The entry reaction of the plant shikimate pathway is subjected to highly complex metabolite-mediated regulation.Plant Cell. 2021; 33: 671-696Crossref PubMed Scopus (39) Google Scholar]. Notably, all the three DHS isoforms present in arabidopsis (Arabidopsis thaliana) are strongly inhibited by caffeate, an intermediate in phenylpropanoid biosynthesis from Phe, indicating that the flux through the shikimate pathway in general is adjusted to meet the demands of specialized metabolite production. A genome-wide ribosome profiling approach revealed that during effector-triggered immunity (ETI) arabidopsis plants specifically induce the biosynthesis pathways for aromatic amino acids and derived specialized metabolites on the level of translation in coordination with increased transcription rates as an additional layer of upregulation [9.Yoo H. et al.Translational regulation of metabolic dynamics during effector-triggered immunity.Mol. Plant. 2020; 13: 88-98Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar]. Thus, the metabolism of aromatic amino acids is an important factor in the interaction between plants and microbes and serves as a toolbox for the production of a variety of tailored active compounds. While the protective function of phytoalexins derived from aromatic amino acids during pathogen attack is well established, their role in recruiting beneficial microbes is just beginning to become clear [7.Jacoby R.P. et al.Recent advances in the role of plant metabolites in shaping the root microbiome.F1000Research. 2020; 9PMC7047909Crossref PubMed Scopus (43) Google Scholar,10.Jacoby R.P. et al.Pinpointing secondary metabolites that shape the composition and function of the plant microbiome.J. Exp. Bot. 2021; 72: 57-69Crossref PubMed Scopus (85) Google Scholar]. Coumarins are polar phenolic compounds produced from Phe via the general phenylpropanoid pathway, and they are ubiquitous in plants [11.Stringlis I.A. et al.The age of coumarins in plant–microbe interactions.Plant Cell Physiol. 2019; 60: 1405-1419Crossref PubMed Scopus (169) Google Scholar]. The synthesis pathway for two coumarins involved in plant–microbe interactions, fratexin and the redox-active sideretin, has been clarified only recently [12.Rajniak J. et al.Biosynthesis of redox-active metabolites in response to iron deficiency in plants.Nat. Chem. Biol. 2018; 14: 442-450Crossref PubMed Scopus (167) Google Scholar,13.Siwinska J. et al.Scopoletin 8-hydroxylase: a novel enzyme involved in coumarin biosynthesis and iron-deficiency responses in Arabidopsis.J. Exp. Bot. 2018; 69: 1735-1748Crossref PubMed Scopus (67) Google Scholar]. In addition, a suite of new publications has contributed to connecting two of the well established physiological functions of coumarins, namely, improving bioavailability of iron in alkaline soils and defense against pathogens (Figure 2B) [11.Stringlis I.A. et al.The age of coumarins in plant–microbe interactions.Plant Cell Physiol. 2019; 60: 1405-1419Crossref PubMed Scopus (169) Google Scholar,14.Tsai H.H. Schmidt W. Mobilization of iron by plant-borne coumarins.Trends Plant Sci. 2017; 22: 538-548Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar]. Using different coumarin-deficient arabidopsis mutant lines in combination with either selected pathogenic and mutualistic microbes or a synthetic microbial community, they revealed the role of coumarins in shaping the root microbiome to improve plant iron nutrition. Specific coumarins are secreted by the roots of arabidopsis plants, which change the composition of the root microbiome by selectively inhibiting the growth of pathogenic microbes but not beneficial strains [15.Stringlis I.A. et al.MYB72-dependent coumarin exudation shapes root microbiome assembly to promote plant health.PNAS. 2018; 115: E5213-E5222Crossref PubMed Scopus (442) Google Scholar, 16.Voges M. et al.Plant-derived coumarins shape the composition of an Arabidopsis synthetic root microbiome.PNAS. 2019; 116: 12558-12565Crossref PubMed Scopus (230) Google Scholar, 17.Harbort C.J. et al.Root-secreted coumarins and the microbiota interact to improve iron nutrition in Arabidopsis.Cell Host Microbe. 2020; 28: 825-837Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. This effect is induced in iron-deficient soils and seems to involve redox-mediated toxicity [16.Voges M. et al.Plant-derived coumarins shape the composition of an Arabidopsis synthetic root microbiome.PNAS. 2019; 116: 12558-12565Crossref PubMed Scopus (230) Google Scholar]. Camalexin is an antifungal sulfur-containing indolic compound synthesized from Trp. It is specific for Brassicaceae and is the most prominent phytoalexin in arabidopsis [18.Glawischnig E. Camalexin.Phytochemistry. 2007; 68: 401-406Crossref PubMed Scopus (215) Google Scholar]. Trp metabolism also produces a series of additional specialized metabolites, including indolic glucosinolates and the auxin indole-3-acetic acid via common intermediates [19.Pastorczyk M. et al.The role of CYP71A12 monooxygenase in pathogen-triggered tryptophan metabolism and Arabidopsis immunity.New Phytol. 2020; 225: 400-412Crossref PubMed Scopus (40) Google Scholar]. Efficient camalexin synthesis without release of active intermediates is achieved by the formation of a camalexin-biosynthetic metabolon, a cytosolic protein complex attached to the endoplasmic reticulum [20.Mucha S. et al.The formation of a camalexin biosynthetic metabolon.Plant Cell. 2019; 31: 2697-2710PubMed Google Scholar]. The pleiotropic drug-resistance transporters PEN3 and PDR12 function redundantly to mediate camalexin secretion [21.He Y. et al.The Arabidopsis pleiotropic drug resistance transporters PEN3 and PDR12 mediate camalexin secretion for resistance to Botrytis cinerea.Plant Cell. 2019; 31: 2206-2222Crossref PubMed Google Scholar]. Camalexin synthesis in the roots is required for recruiting mutualistic microbes to the rhizosphere and, interestingly, it is also a prerequisite for actually receiving growth benefits by potentially growth‐promoting bacterial strains (Figure 2B) [22.Koprivova A. et al.Root-specific camalexin biosynthesis controls the plant growth-promoting effects of multiple bacterial strains.PNAS. 2019; 116: 15735-15744Crossref PubMed Scopus (85) Google Scholar]. The mechanism of this interaction has yet to be discovered. Plants of the Poaceae (such as maize, wheat, and rye) can synthesize large quantities of benzoxazinoids from the Trp precursor indole to regulate belowground as well as aboveground biotic interactions. A number of recent studies highlighted the pivotal role of these heteroaromatic metabolites in shaping the rhizosphere microbiota [23.Hu L. et al.Root exudate metabolites drive plant-soil feedbacks on growth and defense by shaping the rhizosphere microbiota.Nat. Commun. 2018; 9: 2738Crossref PubMed Scopus (668) Google Scholar, 24.Cotton T.E.A. et al.Metabolic regulation of the maize rhizobiome by benzoxazinoids.ISME J. 2019; 13: 1647-1658Crossref PubMed Scopus (149) Google Scholar, 25.Kudjordjie E.N. et al.Maize synthesized benzoxazinoids affect the host associated microbiome.Microbiome. 2019; 7: 59Crossref PubMed Scopus (139) Google Scholar]. Benzoxazinoids serve as toxins towards pathogens and, in addition, as chemoattractants for beneficial microbes, affecting both bacterial and fungal root-associated communities. Soil conditioning even persisted into the next growing season and determined biotic interactions and plant performance in the next generation [23.Hu L. et al.Root exudate metabolites drive plant-soil feedbacks on growth and defense by shaping the rhizosphere microbiota.Nat. Commun. 2018; 9: 2738Crossref PubMed Scopus (668) Google Scholar]. Plants potentially produce hundreds of thousands of different metabolites, and most of them have not yet been characterized [26.Jacobowitz J.R. Weng J.-K. Exploring uncharted territories of plant specialized metabolism in the postgenomic era.Annu. Rev. Plant Bio. 2020; 71: 631-658Crossref PubMed Scopus (59) Google Scholar]. Even with a focus on compounds derived from amino acids, plant specialized metabolism is highly complex and has the potential to provide a high level of specificity during plant–microbe interactions. Due to the high diversity of metabolites across plant species, research on different model and non-model organisms holds the promise of new discoveries. When a plant pathogen begins proliferating in the apoplast, it is usually nutrient-starved and depends on rapid assimilation of nutrients from the host. The plant in turn may reallocate resources for defense or withdraw nutrients from the site of infection. Thus, adaptations in plant nitrogen metabolism upon pathogen attack represent the combined effects of the plant's defense strategy and manipulation by the pathogen to increase nutrient availability. Plants exude 15% of assimilated nitrogen, and amino acids are a major nitrogen currency [27.Venturi V. Keel C. Signaling in the rhizosphere.Trends Plant Sci. 2016; 21: 187-198Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar]. Microbial chemoreceptors recognize a broad variety of amino acids and direct the microbes to the nutrient-rich niches surrounding plant roots [28.Yang Y. et al.Relation between chemotaxis and consumption of amino acids in bacteria.Mol. Microbiol. 2015; 96: 1272-1282Crossref PubMed Scopus (87) Google Scholar]. The ability to use amino acids supplied by the host plant for nutrition might be crucial for establishing symbiotic interactions. Three independent screening approaches identified auxotrophy for specific amino acids as a factor impairing the interaction of growth-promoting Pseudomonas strains with their host arabidopsis [29.Cheng X. et al.Genome-wide analysis of bacterial determinants of plant growth promotion and induced systemic resistance by Pseudomonas fluorescens.Environ. Microbiol. 2017; 19: 4638-4656Crossref PubMed Scopus (37) Google Scholar, 30.Cole B.J. et al.Genome-wide identification of bacterial plant colonization genes.PLoS Biol. 2017; 15e2002860Crossref PubMed Scopus (119) Google Scholar, 31.Liu G. et al.Amino acid homeostasis modulates salicylic acid-associated redox status and defense responses in Arabidopsis.Plant Cell. 2010; 22: 3845-3863Crossref PubMed Scopus (169) Google Scholar]. Amino acid exudation by the plant requires transport across several membranes: (i) between apoplast and cytoplasm for exudation or uptake, (ii) across membranes of intracellular compartments involved in amino acid synthesis, metabolism, and storage (chloroplasts, mitochondria, vacuole), and (iii) between different cells and plant organs to meet the increased local demand caused by microbial interactions (Figure 3). The arabidopsis genome contains about 100 putative amino acid transporters belonging to three major families [32.Tegeder M. Hammes U.Z. The way out and in: phloem loading and unloading of amino acids.Curr. Opin. Plant Biol. 2018; 43: 16-21Crossref PubMed Scopus (68) Google Scholar,33.Dhatterwal P. et al.Promoter profiling of Arabidopsis amino acid transporters: clues for improving crops.Plant Mol. Biol. 2021; 107: 451-475Crossref PubMed Scopus (7) Google Scholar]. Only about 20% of them have been functionally characterized so far [34.Sonawala U. et al.Review: functional linkages between amino acid transporters and plant responses to pathogens.Plant Sci. 2018; 277: 79-88Crossref PubMed Scopus (24) Google Scholar]. While transporters of the amino acid/auxin permease (AAAP) and amino acid polyamine organocation (APC) families and their role in amino acid uptake and secretion by the roots have been known for some time [35.Pratelli R. Pilot G. Regulation of amino acid metabolic enzymes and transporters in plants.J. Exp. Bot. 2014; 65: 5535-5556Crossref PubMed Scopus (251) Google Scholar,36.Dinkeloo K. et al.Update on amino acid transporter functions and on possible amino acid sensing mechanisms in plants.Semin. Cell Dev. Biol. 2018; 74: 105-113Crossref PubMed Scopus (78) Google Scholar], the 'usually multiple acids move in and out transporters' (UMAMIT) family is currently the new center of interest. UMAMITs were originally identified as nodulins required for symbiotic interactions of rhizobia with legumes [37.Gamas P. Use of a subtractive hybridization approach to identify new Medicago truncatula genes induced during root nodule development.MPMI. 1996; 9: 233-242Crossref PubMed Scopus (229) Google Scholar,38.Zhao C. et al.Detailed characterization of the UMAMIT proteins provides insight into their evolution, amino acid transport properties, and role in the plant.J. Exp. Bot. 2021; 72: 6400-6417Crossref PubMed Scopus (11) Google Scholar]. Zhao et al. characterized all 47 UMAMIT genes and proteins found in arabidopsis in detail, including tissue and subcellular localization as well as amino acid transport properties [38.Zhao C. et al.Detailed characterization of the UMAMIT proteins provides insight into their evolution, amino acid transport properties, and role in the plant.J. Exp. Bot. 2021; 72: 6400-6417Crossref PubMed Scopus (11) Google Scholar]. Their results identified a set of particularly stress-responsive UMAMITs as likely candidates for involvement in plant–microbe interactions. UMAMIT14 and UMAMIT18 mediate the radial transport of amino acids in roots and their secretion into the soil [39.Besnard J. et al.UMAMIT14 is an amino acid exporter involved in phloem unloading in Arabidopsis roots.J. Exp. Bot. 2016; 67: 6385-6397Crossref PubMed Scopus (60) Google Scholar]. The transcription factor bZIP11 is required for the induction of these two and an additional three UMAMITs [29,31,34] alongside several nitrate and ammonium transporters and might be targeted by pathogens to secure access to nutrients from their hosts [40.Prior M.J. et al.Arabidopsis bZIP11 is a susceptibility factor during Pseudomonas syringae infection.MPMI. 2021; 34: 439-447Crossref PubMed Scopus (5) Google Scholar]. In addition, the stress-responsive W-BOX motif has recently been identified in the promoter regions of 40 amino acid transporter genes, indicating that regulation by WRKY transcription factors could also play a role [33.Dhatterwal P. et al.Promoter profiling of Arabidopsis amino acid transporters: clues for improving crops.Plant Mol. Biol. 2021; 107: 451-475Crossref PubMed Scopus (7) Google Scholar]. Based on the same promoter profiling approach, induction by the phytohormone salicylic acid (SA) can be postulated for 34 amino acid transporters. In the systemic (noninfected) leaves of arabidopsis plants locally infected with Pseudomonas syringae, the enzymatic pathways catalyzing amino acid synthesis are downregulated on a transcriptional level [41.Schwachtje J. et al.Primed primary metabolism in systemic leaves: a functional systems analysis.Sci. Rep. 2018; 8: 216Crossref PubMed Scopus (53) Google Scholar]. The lowered free contents of most amino acids might help to protect the noninfected leaves by reducing their nutritional value and thus making them less attractive for colonization by pathogens. The role of amino acid exudation in shaping the biochemical ecology of the rhizosphere has frequently been discussed in recent reviews [34.Sonawala U. et al.Review: functional linkages between amino acid transporters and plant responses to pathogens.Plant Sci. 2018; 277: 79-88Crossref PubMed Scopus (24) Google Scholar,36.Dinkeloo K. et al.Update on amino acid transporter functions and on possible amino acid sensing mechanisms in plants.Semin. Cell Dev. Biol. 2018; 74: 105-113Crossref PubMed Scopus (78) Google Scholar,42.Sasse J. et al.Feed your friends: do plant exudates shape the root microbiome?.Trends Plant Sci. 2018; 23: 25-41Abstract Full Text Full Text PDF PubMed Scopus (927) Google Scholar,43.Kim J.-Y. et al.Cellular export of sugars and amino acids: role in feeding other cells and organisms.Plant Physiol. 2021; 187: 1893-1914Crossref PubMed Scopus (17) Google Scholar], but as yet not many mechanistic details are known. Plant amino acid transporters might be targeted by microbes to enhance nutrient availability, and could also be controlled by the plant immune system in order to selectively feed or starve beneficial or pathogenic microbes, respectively. Thus, an important aspect of future research efforts will be to unravel the connections between plant amino acid transporters and resistance or susceptibility to pathogens and pests. Several lines of evidence indicate that plants monitor their amino acid status and interpret specific alterations in metabolic activity, local amino acid concentrations, or transport activities across membranes as a signature of an attacking pathogen (Figure 3A) [34.Sonawala U. et al.Review: functional linkages between amino acid transporters and plant responses to pathogens.Plant Sci. 2018; 277: 79-88Crossref PubMed Scopus (24) Google Scholar]. Overexpression of the amino acid exporters UMAMIT14 and glutamine dumper 1 (GDU1), or the importer cationic amino acid transporter 1 (CAT1), leads to constitutive induction of immune signaling in arabidopsis [28.Yang Y. et al.Relation between chemotaxis and consumption of amino acids in bacteria.Mol. Microbiol. 2015; 96: 1272-1282Crossref PubMed Scopus (87) Google Scholar,31.Liu G. et al.Amino acid homeostasis modulates salicylic acid-associated redox status and defense responses in Arabidopsis.Plant Cell. 2010; 22: 3845-3863Crossref PubMed Scopus (169) Google Scholar,44.Besnard J. et al.Increased expression of UMAMIT amino acid transporters results in activation of salicylic acid dependent stress response.Front. Plant Sci. 2021; 11606386Crossref PubMed Scopus (11) Google Scholar]. By contrast, knockout of lysine histidine transporter 1 (LHT1) or UMAMIT5 (WAT1) increases plant resistance towards a broad spectrum of pathogens [31.Liu G. et al.Amino acid homeostasis modulates salicylic acid-associated redox status and defense responses in Arabidopsis.Plant Cell. 2010; 22: 3845-3863Crossref PubMed Scopus (169) Google Scholar,45.Denancé N. et al.Arabidopsis wat1 (walls are thin1)-mediated resistance to the bacterial vascular pathogen, Ralstonia solanacearum, is accompanied by cross-regulation of salicylic acid and tryptophan metabolism.Plant J. 2013; 73: 225-239Crossref PubMed Scopus (107) Google Scholar]. However, since both of these amino acid transporters also accept additional substrates – such as auxin or the ethylene precursor aminocyclopropane-1- carboxylic acid (ACC) – a disturbance in hormone signaling might be the primary cause for activating defense responses in the knockout lines [45.Denancé N. et al.Arabidopsis wat1 (walls are thin1)-mediated resistance to the bacterial vascular pathogen, Ralstonia solanacearum, is accompanied by cross-regulation of salicylic acid and tryptophan metabolism.Plant J. 2013; 73: 225-239Crossref PubMed Scopus (107) Google Scholar,46.Shin K. et al.Genetic identification of ACC-RESISTANT2 reveals involvement of LYSINE HISTIDINE TRANSPORTER1 in the uptake of 1-aminocyclopropane-1-carboxylic acid in Arabidopsis thaliana.Plant Cell Physiol. 2015; 56: 572-582Crossref PubMed Scopus (63) Google Scholar]. An autoimmune phenotype has also been reported for mutant lines with different modifications in amino acid metabolic enzymes. An RNAseq approach recently identified the mitochondrial branched-chain aminotransferase BCAT1 as a potential regulator of rust infection in wheat [47.Corredor-Moreno P. et al.The branched-chain amino acid aminotransferase TaBCAT1 modulates amino acid metabolism and positively regulates wheat rust susceptibility.Plant Cell. 2021; 33: 1728-1747Crossref PubMed Scopus (23) Google Scholar]. Knockout bcat1 mutants had moderately increased levels of several amino acids and activated a systemic immune response. Transgenic arabidopsis plants overexpressing pepper asparagine synthetase 1 exhibit enhanced resistance to P. syringae pv. tomato DC3000 and Hyaloperonospora arabidopsidis [48.Hwang I.S. et al.Pepper asparagine synthetase 1 (CaAS1) is required for plant nitrogen assimilation and defense responses to microbial pathogens.Plant J. 2011; 67: 749-762Crossref PubMed Scopus (85) Google Scholar]. Cysteine can be synthesized and also metabolized in several different compartments of a plant cell, and this compartmentalization seems to be important for signaling functions during abiotic stress [49.Hildebrandt T.M. et al.Amino acid catabolism in plants.Mol. Plant. 2015; 8: 1563-1579Abstract Full Text Full Text PDF PubMed Scopus (719) Google Scholar,50.Heinemann B. Hildebrandt T.M. The role of amino acid metabolism in signaling and metabolic adaptation to stress-induced energy deficiency in plants.J. Exp. Bot. 2021; 72: 4634-4645Crossref PubMed Scopus (46) Google Scholar]. Recent results indicate that specific pathways in cysteine metabolism might also be relevant for biotic interactions. Overexpression of the mitochondrial cysteine desulfurase NFS1, which degrades cysteine to provide sulfur during FeS cluster synthesis, results in constitutive upregulation of defense-related genes and increased resistance against P. syringae [51.Fonseca J.P. et al.Iron–sulfur cluster protein NITROGEN FIXATION S-LIKE1 and its interactor FRATAXIN function in plant immunity.Plant Physiol. 2020; 184: 1532-1548Crossref PubMed Scopus (11) Google Scholar]. By contrast, knockout of the cytosolic cysteine desulfhydrase DES1 leads to an autoimmune phenotype whereas knockout lines for OAS1 involved in cysteine synthesis in the cytosol are more susceptible to P. syringae [52.Álvarez C. et al.Cysteine homeostasis plays an essential role in plant immunity.New Phytol. 2012; 193: 165-177Crossref PubMed Scopus (127) Google Scholar]. Taken together, these results indicate that increased cysteine degradation in the mitochondria and decreased cysteine degradation in the cytosol both induce a biotic stress response. Homoserine accumulation in the chloroplast due to homoserine kinase deficiency triggers a currently unknown mechanism of downy mildew resistance in arabidopsis [53.van Damme M. et al.Downy mildew resistance in Arabidopsis by mutation of HOMOSERINE KINASE.Plant Cell. 2009; 21: 2179-2189Crossref PubMed Scopus (83) Google Scholar], whereas threonine accumulation renders the plants unsuitable as an infection substrate for the adapted biotrophic pathogen H. arabidopsidis without activating defense responses [54.Stuttmann J. et al.Perturbation of Arabidopsis amino acid metabolism causes incompatibility with the adapted biotrophic pathogen Hyaloperonospora arabidopsidis.Plant Cell. 2011; 23: 2788-2803Crossref PubMed Scopus (94) Google Scholar]. Intriguingly, several other defects i