Towards a functional understanding of the plant metabolome
Introduction
Plants are amazing organic chemists, with the plant metabolome ranging from tens to hundreds of thousands of small molecules. Novel chemistry is being uncovered even in extensively studied plant species such as Arabidopsis thaliana. A great and recent example is the discovery of more than 50 previously unknown triterpene compounds produced by Arabidopsis roots and employed to assemble and modulate root microbiota [1•]. At present, we fail to grasp the full complexity of plant metabolomes and the mode of action for many of the known metabolites. At the same time, new functionalities are being assigned to previously characterised compounds. For example, a recent study demonstrated the role of the amino acid glutamate in the activation of a long-distance, calcium-based plant defence signalling [2,3]. Our review aims to highlight recent studies (focusing on the last five years) that demonstrate the multiple and often unexpected roles of plant metabolites beyond the canonical division of primary and specialized metabolism. To exemplify, we will focus on nucleotides, a group of evolutionarily conserved primary compounds characterised by well-known and emerging functionalities. We will also briefly discuss recent examples of specialized metabolites that defy the simple notion of defence compounds. Finally, we will discuss how emerging biochemical approaches for cell-wide identification of small-molecule-protein complexes, such as small-molecule limited-proteolysis (Lip-SMap) [4••], could be exploited to provide a comprehensive understanding of the plant metabolome.
Section snippets
Nucleotides, from building blocks to signals
Nucleotides are the building blocks of DNA and RNA, although they have many other essential roles in both metabolism and signal transduction. With typically low-to-mid (mM) intracellular concentrations, adenosine triphosphate (ATP) is among the most abundant compounds measured in living cells [5]. ATP is best known for being the energy store used to fuel energy-dependent biochemical reactions, such as metabolic conversions, transport, and cytoskeletal rearrangements. ATP is also a critical
More than defence compounds: regulatory roles of specialized metabolites
Historically, plant secondary (specialized) metabolites were discussed as either attractants or defence compounds enabling plants to tolerate both biotic (e.g., herbivory and pathogen attack) and abiotic (e.g., light and temperature fluctuations) stress conditions. Nowadays, it is clear that specialized metabolites can have other equally essential functionalities.
Carotenoid-derived small molecules (apocarotenoids) are possibly the best example of specialized metabolites and comprise abscisic
From interaction to function
Biological entities, including proteins, nucleic acids, and small molecules, rarely act alone but rather as part of a complex. Along similar lines, metabolites exert most of their function via interaction with a macromolecular partner, most commonly a protein. Therefore, cell-wide identification of metabolite-protein complexes is considered an effective way to learn about metabolite function as attested by the ATP example above [4••,6]. Knowledge of the protein partners is also central for the
Conclusions
There are plenty of small-molecules that remain to be identified and many of the known ones to be functionally characterised. Small molecule identification and characterisation is an exciting research frontier with significant potential for discovery. There are clearly several experimental strategies that could be exploited. Cell-wide identification of protein–metabolite complexes is a promising approach, which nevertheless needs to be complemented with a careful biological validation.
Declaration of interest
None.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
References (45)
- et al.
A map of protein-metabolite interactions reveals principles of chemical communication
Cell
(2018) - et al.
ATPase-modulated stress granules contain a diverse proteome and substructure
Cell
(2016) - et al.
Wounding stress causes rapid increase in concentration of the naturally occurring 2',3'-isomers of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and cAMP) in plant tissues
Phytochemistry
(2014) - et al.
Diadenosine polyphosphates (Ap3A and Ap4A) behave as alarmones triggering the synthesis of enzymes of the phenylpropanoid pathway in Arabidopsis thaliana
FEBS Open Bio
(2011) - et al.
The apocarotenoid beta-cyclocitric acid elicits drought tolerance in plants
iScience
(2019) - et al.
The apocarotenoid metabolite zaxinone regulates growth and strigolactone biosynthesis in rice
Nat Commun
(2019) - et al.
Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses
Cell
(2010) - et al.
Cyclic AMP affinity purification and ESI-QTOF MS-MS identification of cytosolic glyceraldehyde 3-phosphate dehydrogenase and two nucleoside diphosphate kinase isoforms from tobacco BY-2 cells
FEBS Lett
(2001) - et al.
The 1.9 A crystal structure of a nucleoside diphosphate kinase complex with adenosine 3',5'-cyclic monophosphate: evidence for competitive inhibition
J Mol Biol
(1995) - et al.
A specialized metabolic network selectively modulates Arabidopsis root microbiota
Science
(2019)
Glutamate triggers long-distance, calcium-based plant defense signaling
Science
GLUTAMATE RECEPTOR-LIKE genes mediate leaf-to-leaf wound signalling
Nature
Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli
Nat Chem Biol
Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP
Nat Commun
ATP as a biological hydrotrope
Science
Identification of a plant receptor for extracellular ATP
Science
Extracellular ATP Acts on jasmonate signaling to reinforce plant defense
Plant Physiol
Extracellular ATP, a danger signal, is recognized by DORN1 in Arabidopsis
Biochem J
Extracellular ATP elicits DORN1-mediated RBOHD phosphorylation to regulate stomatal aperture
Nat Commun
Extracellular ATP shapes a defense-related transcriptome both independently and along with other defense signaling pathways
Plant Physiol
Changes in the Arabidopsis thaliana proteome implicate cAMP in biotic and abiotic stress responses and changes in energy metabolism
Int J Mol Sci
Cyclic AMP deficiency negatively affects cell growth and enhances stress-related responses in tobacco Bright Yellow-2 cells
Plant Mol Biol
Cited by (29)
Plant stress response and adaptation via anthocyanins: A review
2023, Plant StressProteinogenic dipeptides, an emerging class of small-molecule regulators
2023, Current Opinion in Plant BiologyRice metabolic regulatory network spanning the entire life cycle
2022, Molecular PlantCitation Excerpt :They can, furthermore, influence other aspects of plant growth, development, and nutritional quality that are important in rice production, so they have great potential as molecular breeding targets. To sum up, it is necessary to study the changes of metabolites and their underlying regulatory mechanisms from a more macroscopic perspective, namely the "metabolome," and the plant metabolome currently plays a vital role in modern plant biology research and biotechnology applications (Luo, 2015; Kosmacz et al., 2020). Thanks largely to the establishment of a high-throughput metabolite detection technology for rice (Chen et al., 2013), metabolome detection has been applied to many different aspects of rice biology.
Multiomics approaches for the improvements of postharvest systems
2021, Postharvest Handling: A Systems ApproachSpecialized metabolism and development: An unexpected friendship
2021, Current Opinion in Plant BiologyExperimental methods for dissecting the terraincognita of protein-metabolite interactomes
2021, Current Opinion in Systems BiologyCitation Excerpt :Further progress in identifying and quantifying metabolites and proteins will be instrumental in dissecting the composition and dynamics of protein-metabolite interactomes and consequently a comprehensive functional annotation of metabolomes [14,19].