Metabolic Basis Research Articles

Metabolomics profiling reveals p-aminobenzoic acid enhances resistance to Fusarium head blight in wheat

Fusarium head blight (FHB) not only causes severe yield losses but also mycotoxin contamination in wheat, posing a serious threat to food security and public health. The mechanisms of resistance to FHB in wheat are critical for effective prevention and control of the pathogen. In this research, we investigated and analyzed the metabolite changes induced by FHB colonization in the FHB-resistant cultivar Lianmai12 through Fusarium graminearum inoculation and mock inoculation. A total of 1001 metabolites were detected, 109 of which were significantly changed due to FHB infection. The majority of these 109 metabolites belonged to alkaloids, flavonoids, phenolic acids, lipids and organic acids. The most enriched KEGG pathways were plant hormone signal transduction and phenylpropanoid biosynthesis, which may constitute the major defence responses to FHB challenge. The metabolite p-aminobenzoic acid (PABA) significantly suppressed the growth of mycelia and the production of conidia in vitro. Further studies revealed that spraying PABA at early anthesis on wheat spikes reduced the development of FHB disease. These results provide preliminary insights into the metabolic basis of resistance in Lianmai12 and will be beneficial in the development of potential biocontrol agents against FHB.Graphical

Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma

Primary liver cancer is a common malignant tumor of the digestive system, with hepatocellular carcinoma (HCC) being the most prevalent type. It is characterized by high malignancy, insidious onset, and a lack of specific early diagnostic and therapeutic markers, posing a serious threat to human health. The occurrence and development of HCC are closely related to its metabolic processes. Similar to other malignant tumors, metabolic reprogramming occurs extensively in tumor cells, with glucose metabolism reprogramming being particularly prominent. This is characterized by abnormal activation of glycolysis and inhibition of oxidative phosphorylation and gluconeogenesis, among other changes. Glucose metabolism reprogramming provides intermediates and energy for HCC to meet its demands for rapid growth, proliferation, and metastasis. Additionally, various enzymes and signaling molecules involved in glucose metabolism reprogramming play irreplaceable roles. Therefore, regulating key metabolic enzymes and pathways in these processes is considered an important target for the diagnosis and treatment of HCC. This paper reviews the current status and progress of glucose metabolism reprogramming in HCC, aiming to provide new insights for the diagnosis, detection, and comprehensive treatment strategies of HCC involving combined glucose metabolism intervention in clinical settings.

Dysregulated hepatic alcohol metabolism: a key factor involved in the pathogenesis of alcohol-associated liver disease.

Alcohol use disorder is a major risk factor for alcohol-associated liver disease (ALD), characterized by reduced hepatic alcohol dehydrogenase (ADH) activity, increased body burden of alcohol and its nonoxidative metabolism to fatty acid ethyl esters (FAEEs). However, the mechanism(s) underlying ALD remain unclear. This study investigated metabolic basis and mechanism(s) of ALD in chronic ethanol (EtOH) fed hepatic ADH1-deficient (ADH-) deer mice administered with a single dose of binge EtOH with/without FAEEs. Hepatic ADH- and ADH normal (ADH+) deer mice fed chronic EtOH daily for 3 months, followed by a single dose of binge EtOH [3g/kg body weight (BW)] with/without FAEEs (100 mg/kg BW), one week prior to euthanasia. Blood alcohol and acetaldehyde and liver injury markers in the plasma, hepatic FAEEs, lipids and inflammatory markers were analyzed. Hepatic histology, ultrastructure, protein/mRNA expression of genes involved in alcohol metabolism and lipogenesis, cAMP, phosphodiesterase (PDE) activity, and AMPKα signaling were assessed. Blood alcohol, hepatic lipids and FAEEs, inflammation, oxidative stress, and the expression of lipogenic proteins/genes were significantly increased in various chronic EtOH-fed groups of ADH- vs. ADH+ deer mice. Additionally, hepatic cAMP levels were reduced, while PDE activity and plasma transaminases were elevated. Binge EtOH with/without FAEEs did not significantly exacerbate the liver injury in chronic EtOH-fed ADH- as well as ADH+ deer mice. Overall, an increased body burden of EtOH and endogenously formed FAEEs due to hepatic ADH deficiency, along with dysregulated cAMP and AMPKα signaling, could be the determining factors for EtOH-induced liver injury leading to ALD.

The metabolic basis of cancer-related fatigue.

Although we are all familiar with the sensation of fatigue, there are still profound divergences on what it represents and its mechanisms. Fatigue can take various forms depending on the condition in which it develops. Cancer-related fatigue is considered a symptom of exhaustion that is often present at the time of diagnosis, increases in intensity during cancer therapy, and does not always recede after completion of treatment. It is usually attributed to the inflammation induced by damage-associated molecular patterns released by tumor cells during cancer progression and in response to its treatment. In this review, we argue that it is necessary to go beyond the symptoms of fatigue to understand its nature and mechanisms. We propose to consider fatigue as a psychobiological process that regulates the behavioral activities an organism engages in to satisfy its needs, according to its physical ability to do so and to the capacity of its intermediary metabolism to exploit the resources procured by these activities. This last aspect is critical as it implies that these metabolic aspects need to be considered to understand fatigue. Based on the findings we have accumulated over several years of studying fatigue in diverse murine models of cancer, we show that energy metabolism plays a key role in the development and persistence of this condition. Cancer-related fatigue is dependent on the energy requirements of the tumor and the negative impact of cancer therapy on the mitochondrial function of the host. When inflammation is present, it adds to the organism's energy expenses. The organism needs to adjust its metabolism to the different forms of cellular stress it experiences thanks to specialized communication factors known as mitokines that act locally and at a distance from the cells in which they are produced. They induce the subjective, behavioral, and metabolic components of fatigue by acting in the brain. Therefore, the targeting of mitokines and their brain receptors offers a window of opportunity to treat fatigue when it is no longer adaptive but an obstacle to the quality of life of cancer survivors.

717 Metabolic basis of post-infectious sequelae after Ebola virus disease

717 Metabolic basis of post-infectious sequelae after Ebola virus disease

Fitness and adaptive evolution of a Rhodococcus sp. harboring dioxin-catabolic plasmids.

Catabolic plasmids are critical factors in the degradation of recalcitrant xenobiotics, such as dioxins. Understanding the persistence and evolution of native catabolic plasmids is pivotal for controlling their function in microbial remediation. Here, we track the fitness and evolution of Rhodococcus sp. strain p52 harboring dioxin-catabolic plasmids under nonselective conditions without contaminant. Growth curve analysis and competition experiments demonstrated that pDF01 imposed fitness costs, whereas pDF02 conferred fitness benefits. During stability tests, pDF01 tended to be lost from the population, while pDF02 maintained at least one copy in the cell until proliferation of the 400th generation. Genome-wide gene expression profiling combined with codon usage bias analysis revealed that the high expression of pDF01 genes involved in dibenzofuran catabolism and regulation caused metabolic burdens. In contrast, potential cooperation between the pDF02-encoded short-chain dehydrogenase/reductase family oxidoreductase and the redox cofactor mycofactocin, which synthetic genes are located on the chromosome, may explain the benefit of pDF02. The fitness cost imposed by pDF01 was alleviated during adaptive evolution and was associated with the transcriptional downregulation of the dibenzofuran degradation genes on pDF01, and the global regulation of genome-wide gene expression involving basic metabolism, transport, and signal transduction. This study broadens our understandings on the persistence and evolution of dioxin-catabolic mega-plasmids, thus paving the way for the bioremediation of recalcitrant xenobiotic pollution in the environment.

The Epigenetic Machinery and Energy Expenditure: A Network to Be Revealed.

Mendelian disorders of the epigenetic machinery (MDEMs) include a large number of conditions caused by defective activity of a member of the epigenetic machinery. MDEMs are characterized by multiple congenital abnormalities, intellectual disability and abnormal growth. that can be variably up- or down-regulated. Background/Objectives: In several MDEMs, a predisposition to metabolic syndrome and obesity since childhood has been reported. Methods: To investigate the metabolic bases of this abnormal growth, we collected physical data from a heterogeneous pool of 38 patients affected by MDEMs. Thirty-five patients performed indirect calorimetry (as a measure of resting energy expenditure, REE) and blood tests to monitor plasmatic nutritional parameters. Conclusions: Although limited by a small-sized and heterogeneous sample, our study demonstrates a linear correlation between REE and physical parameters, OFC, height and weight, and observed a slight imbalance on several plasmatic spies of metabolic syndrome predisposition. Furthermore, we demonstrated a significantly higher REE in Sotos Syndrome type 1 patients compared to the controls, which resulted independent from height, suggesting that impaired metabolism in these patients may go beyond overgrowth.

Zooming into CTC black-tea wine metabolites: A GC-MS-based study

This research was designed to propose a report on fermentation metabolomics of CTC (crush-tear-curl) tea wine (TW), a yeast-fermented broth of sugared CTC black tea infusion. The gas chromatography-mass spectrometry analysis of the tea wine revealed the presence of thirty-five metabolites, including the major compound glycerine with some potential antioxidant molecules and other bioactive agents (4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-; furfural; furfuryl alcohol; succinic acid; levulinic acid; palmitic acid; tyrosol, pyruvaldehyde; and 1-hexadecanol). The role of metabolites in the physicochemical, biochemical, and medicinal properties of TW has been discussed. Biomolecules responsible for the flavour of TW were as follows: glycerine derivatives; pyruvaldehyde; furfural; furfuryl alcohol; acetic, levulinic, succinic, and palmitic acids, etc. – which might develop a sweet, caramel-like, astringent, slightly sour and wine-like flavour and taste. Furthermore, on the basis of yeast metabolism, possible biosynthesis pathways of metabolites were designed aiming for fermentation metabolomics. The outcome of this study cross-verified physicochemical, biochemical, and medicinal properties of TW suggesting its acceptability. As the fields of both wine research and tea science continue to evolve, the findings of this study may encourage fermentation technology for product development from tea that may also boost the growth of the tea industry.

IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4+ Tcell proliferation.

Interleukin (IL)-7 promotes Tcell expansion during lymphopenia. We studied the metabolic basis in CD4+ Tcells, observing increased glucose usage for nucleotide synthesis and oxidation in the tricarboxylic acid (TCA) cycle. Unlike other TCA metabolites, glucose-derived citrate does not accumulate upon IL-7 exposure, indicating diversion into other processes. In agreement, IL-7 promotes glucose-dependent histone acetylation and chromatin accessibility, notable at the loci of the amino acid-sensing Ragulator complex. Consistently, the expression of its subunit late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (LAMTOR5) is promoted by IL-7 in a glucose-dependent manner, and glucose availability determines amino acid-dependent mechanistic target of rapamycin (mTOR) activation, confirming integrated nutrient sensing. LAMTOR5 deletion impairs IL-7-mediated Tcell expansion, establishing that glycolysis in the absence of Ragulator activation is insufficient to support this. Clinically, CD4+ Tcells from stem cell transplant recipients demonstrate coordinated upregulation of glycolytic and TCA cycle enzymes, amino acid-sensing machinery, and mTOR targets, highlighting the potential to therapeutically target this pathway to fine-tune lymphopenia-induced Tcell proliferation.

The Role of Algal Symbiont Growth in Driving the Thermal Responses of a Widespread Photosymbiotic Ciliate

Understanding the impacts of climate change on ecosystems remains a major contemporary research theme in the biosciences. However, the role of mixotrophs, organisms that combine autotrophic and heterotrophic processes to grow and reproduce, as important determinants of the thermal responses of ecosystems and their services is largely unresolved. In particular, photosymbioses, ubiquitous mixotrophic associations in which autotrophs reside within heterotrophic hosts, are known to play key roles in global biodiversity and carbon cycling. While specific impacts, particularly in the coral-zooxanthellae interaction, are thoroughly documented, ecologists lack a general theoretical framework describing the impacts of temperature change on photosymbiotic interactions. Here, I apply principles of the metabolic theory of ecology to assess the metabolic basis of the temperature-induced disruption of photosymbiosis in the microbial <i>Paramecium bursaria - Chlorella</i> spp. association. In contrast to the general prediction that net autotrophy should decrease with temperature, this microbial photosymbiosis harboured larger algal symbiont populations and consumed fewer prey with warming, suggestive of increased net autotrophy with warming - a pattern that held across strains isolated from three different continents. This observation appeared to be a simple consequence of the response of symbiont growth rate. I conclude that a metabolic framework for photosymbiosis may prove insightful, but the ecological dynamics of the associations (e.g. mixotrophic strategy) must be considered in tandem.

Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study.

X-linked hypophosphatemia (XLH) is a rare disorder characterized by elevated levels of fibroblast growth factor 23 (FGF-23), leading to hypophosphatemia and complications in diagnosis due to its clinical heterogeneity. Metabolomic analysis, which examines metabolites as the final products of cellular processes, is a powerful tool for identifying in vivo biochemical changes, serving as biomarkers of pathological abnormalities, and revealing previously uncharted metabolic pathways. A multicenter cross-sectional case-control study of adult patients diagnosed with XLH was conducted. Serum metabolomic analysis was performed with an Ultra-Performance Liquid Chromatography equipment (UPLC) coupled to a high-resolution mass spectrometer (MS). An analysis of metabolic pathways using MetaboAnalyst version 5.0 and a quantitative enrichment analysis (QEA) was performed. We employed multivariate statistical models, including a principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) regression model. A cohort of 20 XLH patients and 19 control subjects were recruited. A total of 104 metabolites were identified. The differential metabolites identified included glycine, taurine, hypotaurine, phosphoethanolamine, pyruvate, guanidoacetic acid, serine, succinate, 2-aminobutyric acid, glutamine, 2-hydroxyvaleric acid, methionine, ornithine, phosphorylcholine, hypoxanthine, lysine, and N-methylnicotinamide. Enrichment analysis identified disturbances in key metabolic pathways, including phosphatidylethanolamine biosynthesis, sphingolipid metabolism, and phosphatidylcholine biosynthesis. Additionally, pathways related to cysteine metabolism, glycolysis, and pyruvate metabolism. This study identified significant differences in the metabolic profiles of individuals with XLH compared to healthy controls. These findings enhance understanding of potential pathogenic mechanisms and offer a metabolic basis for further in-depth investigations into XLH.

Activity-Based Proteome Profiling of Serum Serine Hydrolases: Application in Pediatric Abusive Head Trauma.

Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial hemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes. Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation, and neuronal signaling. Here, we investigated activity-based protein profiling (ABPP) coupled to liquid chromatography-mass spectrometry (LC-MS) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS). Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism. To our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.

Unveiling Tissue-Specific RNA Landscapes in Mouse Organs During Fasting and Feeding Using Nanopore Direct RNA Sequencing.

Understanding tissue-specific RNA landscapes is essential for uncovering the functional mechanisms of key organs in mammals. However, current knowledge remains limited, as short-read RNA sequencing-the predominant method for assessing gene expression-depends on incomplete gene annotations and struggles to resolve the diverse transcripts produced by genes. To address these limitations, an integrative approach combining nanopore direct RNA sequencing (DRS), ATAC-Seq, and short-read RNA-seq is used. This method enabled the analysis of RNA landscapes across major mouse organs under fasting and fed conditions, representing two extremes of the caloric cycle. This study uncovered tens of thousands of novel transcripts and identified hundreds of genes with tissue-specific expression, revealing additional layers of regulated pathways within each organ that conventional short-read RNA-seq cannot resolve. By profiling transcript expression across multiple organs under identical conditions, it is conducted comparative analyses exposing significant differences in transcript isoforms and regulations. Moreover, nanopore DRS revealed dynamic changes in poly(A) tail length and m6A modifications of transcripts, many regulated in a tissue-specific manner. These changes likely contribute to functional differentiation and metabolic specialization of various organs. Collectively, this findings reveal previously unrecognized layers of gene regulation, offering new insights into the metabolic basis of organ function.

Widely Targeted Metabolomics Revealed the Metabolic Basis of Physiological Function and Flavor of Natto.

Background: Natto is a fermented product derived from soybeans through the action of Bacillus subtilis natto, possessing various pharmacological and health-promoting properties. However, due to the absence of large-scale and systematic investigations into its metabolite profile, the mechanisms governing the biological functions and flavor characteristics of natto remain incompletely elucidated. Methods: In this study, a comprehensive, widely targeted metabolome analysis was conducted using UHPLC-MS/MS to compare soybeans and natto. Results: A total of 569 metabolites were identified, of which 160 exhibited differential expression between natto and soybeans, including 28 amino acids and their derivatives, 19 flavonoids, 18 alkaloids, and 10 nucleotides and their derivatives. Pathway enrichment analysis further demonstrated significant differences in the metabolic pathways between natto and soybeans, with these 160 differentially expressed metabolites primarily distributed across 40 metabolic pathways. KEGG pathway enrichment analysis of natto metabolites revealed that the majority of these mapped to three key metabolic pathways. Variations in the content of flavonoids and alkaloids, as well as changes in amino acid and saccharide composition and abundance, were found to collectively contribute to the distinctive flavor and biological functionality of natto. Conclusions: This study lays the foundation for future efforts to enhance the quality of natto.

Molecular Basis of Lipid Metabolism in Oryza sativa L.

Lipids are the basic biological molecules in plants, serving as glycerolipids for cell membranes and triacylglycerols as an energy source. Fatty acids are the major components of plant lipids. Both lipids and fatty acids significantly influence rice quality. Recent studies, through genetic analysis, have made significant progress in uncovering the functional mechanisms and regulatory pathways of lipid metabolism including the biological synthesis and degradation of fatty acids, glycerolipids, and triacylglycerols in rice. Meanwhile, quantitative trait loci (QTLs) identified by analyzing the natural variations of the composition and contents of lipids and fatty acids have been integrated and represented on 12 chromosomes. Lipids play multifaceted roles in the growth and development and stress response of rice. Through metabolic engineering and gene-editing technologies, significant advancements have been made in improving the lipid content in rice grains. These studies highlight the understanding the of molecular basis of lipid metabolism and lay a substantial basis for the genetic improvement of rice quality.

Changes in the Basic Metabolic Rate of the Crew under conditions of Eight Months Isolation in a Hermetic Object with a Moderately Hypercapnic Artificial Gas Environment. Message 1

Within the framework of the SIRIUS international project, a study of the basic metabolism of a gender-mixed crew in a sealed object with a moderately high content of carbon dioxide in the artificial atmosphere was conducted. Using mathematical methods, we estimated the basic metabolic rate of a crew of 5 people (3 men and 2 women) at rest for 240 days of isolation when simulating a flight to the Moon in the “SIRIUS-21” experiment. The period of isolation lasted from 4.11.2021 to 3.07.2022. BMR studies were performed twice in the background (on –38–35, –6 days), 7 times during the isolation period (23–25, 50–52, 84–86, 110–112, 154–156, 181–183, 222–224 day) and twice during the aftereffect period (+1–2, +8–9 days). It was found that the basic metabolism in isolation decreased by an average of 6 kcal/kg of body weight per day compared with natural environmental conditions. The crew was isolated from the effects of seasonal lighting changes in a sealed facility, the Ground-Based Medical and Technical Facility (NEK) of the Scientific Research Center of the Russian Federation - Institute of Biomedical Problems of the Russian Academy of Sciences, which does not have portholes, and where artificial lighting was created without seasonal changes. Inside the NEK, the comfort temperature was constantly maintained at +21–23 degrees Celsius and an artificial gas environment was formed, in which the oxygen content was maintained at 21%, carbon dioxide no more than 0.35%. In conditions of isolation from the action of these geophysical environmental factors, seasonal fluctuations in basal metabolism with a wave span of an average of 4 kcal /kg of body weight per day were detected: in the spring calendar season, the level of basal metabolism increased relative to the winter season. Seasonal local maximums and minimums of the basic exchange level for 2 calendar seasons (winter 2021/2022 and in spring 2022) were determined for each of the volunteers. The results obtained in this work can be applied in the field of space physiology to clarify the calculated oxygen reserves and caloric content of the crew’s rations for a long-term space mission, as well as in the design and programming of life support systems and thermal management systems for inhabited hermetic objects.

Computational journey to unveil organophosphorothioate pesticides’ metabolism: A focus on chlorpyrifos and CYP2C19 mutational landscape

Organophosphorothioates (OPT) are pesticides impacting human, animal and environmental health. They enter the environment worldwide, primarily due to their application as insecticides. OPTs are mainly neurotoxic upon bioactivation and inhibition of brain and serum acetylcholinesterase (AChE). Although OPTs are meant to target insects, they are potentially toxic to many other species (including humans), posing risks to non-target organisms and ecosystems. Certain cytochromes P450 (CYP) promote OPTs bioactivation, forming the corresponding oxon metabolites, while others catalyse their detoxification. Understanding the molecular basis of such a bivalent fate may help to clarify the toxicity of OPTs in living organisms, with far-reaching consequences to understand their impact on living organisms and improve risk assessment, to cite but a few. However, although crucial, the underpinning mechanisms still lay unclear. Here, a validated computational pipeline revealed the molecular reasons underlying the differential metabolism of chlorpyrifos in humans by CYP2C19, a primal route of detoxification, and its bioactivation by CYP2B6. The analysis drew the diverse occupancy of the CYP pocket and orientation to the heme group as a convincing evidence-based explanation for the opposite transformation. Moreover, this study explored the impact of CYP2C19 mutational landscape giving a blueprint to unveil the molecular basis of OPTs metabolism and toxicological implications from an inter-individual perspective. Taken together, the outcome described for the first time to the best of our knowledge a structural rationale for the bioactivation/detoxification of OPTs improving the current understanding of their toxicity from a molecular standpoint.

Structural analysis of the siderophore-interacting protein from Vibrio anguillarum and its implications in classification of Vibrio homologs

Bacteria secrete siderophores to sequester the scarce iron in the environments, then the iron is transported into the cell in a siderophore-complexed form, which can be released by siderophore-interacting protein (SIP). Vibrio species comprise an array of serious pathogens, whose iron releasing process by SIP remains poorly understood. Herein, we report the high-resolution (1.2 Å) structure of Vibrio anguillarum SIP (VaSIP) in complex with FAD, representing the first structure of Vibrio SIP. VaSIP consists of a FAD-bound β-barrel domain and a Rossmann-fold domain connected by a linker, like other subgroup I SIPs. FAD is bound to the inter-domain cavity by aromatic stacking and hydrogen bonding interactions. Structural comparison indicated a modified NAD(P)H-binding motif (DxTA–EVL–GE) for subgroup I SIPs. The putative siderophore-binding pocket of VaSIP contains three lysines to form the basic triad to bind siderophore. Phylogenetic analysis shows Vibrio SIPs are mainly divided into two clades, represented by VaSIP and Vibrio cholerae ViuB, respectively. Interestingly, the two clades adopt distinct siderophore-binding basic triads, suggesting functional divergence among Vibrio SIPs. Our results shed light on the structural and phylogenetic characteristics of Vibrio SIPs, providing molecular basis for understanding Vibrio iron metabolism and designing anti-Vibrio drugs.

Volatilome-based GWAS identifies OsWRKY19 and OsNAC021 as key regulators of rice aroma

Aromatic rice is globally favored for its distinctive scent, which not only increases its nutritional value but also enhances its economic importance. However, apart from 2-acetyl-1-pyrroline (2-AP), the metabolic basis of aroma remains to be clarified, and the genetic basis of the accumulation of fragrance metabolites is largely unknown. In this study, we revealed 2-AP and fatty acid-derived volatiles (FAVs) as key contributors to rice aroma by combining aroma rating with molecular docking. Using a volatilome-based genome-wide association study, we identified two regulatory genes that determine the natural variation of these fragrance metabolites. Genetic and molecular analyses showed that OsWRKY19 not only enhances fragrance by negatively regulating OsBADH2 but also improves agricultural traits in rice. Furthermore, we revealed that OsNAC021 negatively regulates FAV contents via the lipoxygenase pathway, and its knockout resulted in over-accumulation of grain FAVs without a yield penalty. Collectively, our study not only identifies two key regulators of rice aroma but also provides a compelling example about how to deciphering the genetic regulatory mechanisms that underlie rice fragrance, thereby paving the way for the creation of aromatic rice varieties.

A metabolic roadmap of waxy corn flavor

As well as being a popular vegetable crop worldwide, waxy corn represents an important amylopectin source, but little is known about its breeding history and flavor characteristics. In this study, through comparative-omic analyses between 318 diverse waxy corn and 507 representative field corn inbred lines we revealed that many metabolic pathways and genes exhibited selection characteristics during the breeding history of waxy corn, contributing to the divergence between waxy and field corn. We showed that waxy corn is not only altered in its glutinous property but also its sweetness, aroma, and palatability are all significantly affected. A substantial proportion (43%) of flavor-related metabolites have pleiotropic effects, affecting both flavor and yield characteristics, and 27% of these metabolites are related to antagonistic outcomes on yield and flavor. Furthermore, through multiple concrete examples, we demonstrated how yield and quality are coordinately or antagonistically regulated at the genetic level. In particular, some sweet molecules, such as DIMBOA and raffinose, which do not participate in the starch biosynthesis pathway, were identified as potential targets for breeding a new type of “sweet-waxy” corn. Taken together, our findings shed light on the historical selection of waxy corn and demonstrate the genetic and metabolic basis of waxy corn flavor, collectively providing valuable resources and knowledge for future crop breeding for improved nutritional quality.