Chemical Stability of Thiol and Flavanol Sulfonation Products during Wine Aging Conditions.

Bisulfite (HSO3-) is the predominant form of sulfur dioxide, present as free and bound to wine relevant electrophiles under wine acidic pH. While sulfonation reactions of flavanols and thiols have been recently reported as key for wine preservation against oxidation, the transient mechanisms and physicochemical parameters responsible for that remain unknown. In the present study, sulfonation reaction kinetics of thiols and flavanols were monitored under simulated wine aging conditions. The reaction products were then characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and their chemical stability during time was determined by 1H NMR spectroscopy. Thiol and flavanol sulfonation reaction yields were both promoted by the presence of iron and oxygen, while their chemical stability was confirmed under the same conditions. The sulfonation derivatives of epicatechin and cysteine were synthesized and quantified in young and aged wines. Higher concentrations were reported for both metabolites in older wines, indicating their participation on the strongly bound sulfur dioxide fraction. These findings offer new prospects for more precise use of sulfur dioxide in winemaking.

Multivariate prediction of Saliva Precipitation Index for relating selected chemical parameters of red wines to the sensory perception of astringency.

Astringency is an essential sensory attribute of red wine closely related to the saliva precipitation upon contact with the wine. In this study a data matrix of 52 physico-chemical parameters was used to predict the Saliva Precipitation Index (SPI) in 110 Italian mono-varietal red wines using partial least squares regression (PLSr) with variable selection by Variable Importance for Projection (VIP) and the significance of regression coefficients. The final PLSr model, evaluated using a test data set, had 3 components and yielded an R2test of 0.630 and an RMSEtest of 0.994, with 19 independent variables whose regression coefficients were all significant at p < 0.05. Variables selected in the final model according to the decreasing magnitude of their absolute regression coefficient include the following: Procyanidin B1, Epicatechin terminal unit, Total aldehydes, Protein content, Vanillin assay, 520 nm, Polysaccharide content, Epigallocatechin PHL, Tartaric acid, Volatile acidity, Titratable acidity, Catechin terminal unit, Proanthocyanidin assay, pH, Tannin-Fe/Anthocyanin, Buffer capacity, Epigallocatechin PHL gallate, Catechin + epicatechin PHL, and Tannin-Fe. These results can be used to better understand the physico-chemical relationship underlying astringency in red wine.

Metabolic Fingerprinting of Muscat of Alexandria Grape Musts during Industrial Alcoholic Fermentation Using HS-SPME and Liquid Injection with TMS Derivatization GC-MS Methods.

Muscat of Alexandria is one of the most aromatic grape cultivars, with a characteristic floral and fruity aroma, producing popular appellation of origin wines. The winemaking process is a critical factor contributing to the quality of the final product, so the aim of this work was to study metabolomic changes during the fermentation of grape musts at the industrial level from 11 tanks, 2 vintages, and 3 wineries of Limnos Island. A Headspace Solid-Phase Microextraction (HS-SPME) and a liquid injection with Trimethylsilyl (TMS) derivatization Gas Chromatography-Mass Spectrometry (GC-MS) methods were applied for the profiling of the main volatile and non-volatile polar metabolites originating from grapes or produced during winemaking, resulting in the identification of 109 and 69 metabolites, respectively. Multivariate statistical analysis models revealed the differentiation between the four examined time points during fermentation, and the most statistically significant metabolites were investigated by biomarker assessment, while their trends were presented with boxplots. Whilst the majority of compounds (ethyl esters, alcohols, acids, aldehydes, sugar alcohols) showed an upward trend, fermentable sugars, amino acids, and C6-compounds were decreased. Terpenes presented stable behavior, with the exception of terpenols, which were increased at the beginning and were then decreased after the 5th day of fermentation.

Flint glass bottles cause white wine aroma identity degradation.

Due to marketing recommendations, white wines are often bottled in flint glass to improve aesthetics and showcase wine color. Although this practice is known to cause a wine fault, the influence of light on the fruity and flowery aromatic profile of wine is unknown. The aim of this study was to investigate the changes to the white wine volatilome under typical supermarket shelf conditions, using 1,052 bottles of 24 white wines. After only 7 d of shelf life in flint glass bottles, a dramatic loss in terpenes (10 to 30%) and norisoprenoids (30 to 70%) was recorded, whereas colored glass bottles did not evidence such behavior even after 50 d, and darkness preserved the wine's fruity and flowery aromatic integrity. We also proposed an alternative mechanism for the insurgence of the lightstrike off-odor, which takes the varietal aroma loss into account. In light of this understanding of the flint glass negative impact on white wine aroma identity and sensorial character, this packaging should be strongly discouraged. The same findings should be valid for a wide range of several daily consumed foodstuff where transparent packaging is used.

Measurement of the Effect of Accelerated Aging on the Aromatic Compounds of Gewürztraminer and Teroldego Wines, Using a SPE-GC-MS/MS Protocol.

Knowing in detail how the white and red wine aroma compounds behave under various storage conditions and especially at high temperature is important in order to understand the changes occurring to their sensorial character during the shelf life. The initial aim of this work was to develop and validate a fast, modern, robust, and comprehensive protocol for the quantification of 64 primary, secondary, and tertiary volatile compounds by using solid-phase extraction (SPE) cartridges in sample preparation and fast GC-MS/MS (gas chromatography-tandem mass spectrometry assay) in analysis. The protocol was applied to a study of the behavior of seven Gewürztraminer and seven Teroldego wines stored in anoxia at 50 °C for 2.5 and 5 weeks. The results demonstrated a sharp decrease of the main linear terpenes linalool, geraniol, and nerol and the consequent increase of the cyclic ones, such as α-terpineol and 1,8-cineole; the increase of the C13-norisoprenoids 1,1,6,-trimethyl-1,2-dihydronapthalene (TDN), and ß-damascenone and the C10 norisoprenoid safranal; the hydrolysis of acetates and linear esters; and the increase of some branched-chain esters. In red wines, a moderate increase was observed for some lactones. Some unwanted compounds, such as 2-aminoacetophenone (2-AAP), showed a notable increase in some Gewürztraminer wines, exceeding the olfactory threshold.

Modeling grape taste and mouthfeel from chemical composition.

This research aims at predicting sensory properties generated by the phenolic fraction (PF) of grapes from chemical composition. Thirty-one grape extracts of different grape lots were obtained by maceration of grapes in hydroalcoholic solution; afterward they were submitted to solid phase extraction. The recovered PFs were reconstituted in a wine model. Subsequently the wine models, containing the PFs, were sensory (taste, mouthfeel) and chemically characterized. Significant sensory differences among the 31 PFs were identified. Sensory variables were predicted from chemical parameters by PLS-regression. Tannin activity and concentration along with mean degree of polymerization were found to be good predictors of dryness, while the concentration of large polymeric pigments seems to be involved in the "sticky" percept and flavonols in the "bitter" taste. Four fully validated PLS-models predicting sensory properties from chemical variables were obtained. Two out of the three sensory dimensions could be satisfactorily modeled. These results increase knowledge about grape properties and proposes the measurement of chemical variables to infer grape quality.

LC-MS-Based Metabolomics Discriminates Premium from Standard Chilean cv. Cabernet Sauvignon Wines from Different Valleys.

Cabernet Sauvignon grapes in Chile, mainly grown between the 30° S and 36° S, account for more than 30% of Chilean wine production, and yield wines with different characteristics which influence their quality. The aim of this study was to apply a liquid chromatography-mass spectrometry (LC-MS)-based metabolomic protocol to investigate the quality differentiation in a sample set of monovarietal wines from eight valleys covering 679 km of the north-south extension. All samples were produced using a standardized red winemaking process and classified according to a company categorization in two major groups: premium and standard, and each group in two subcategories. The results pointed out that N-containing metabolites (mainly small peptides) are promising biomarkers for quality differentiation. Moreover, the premium wines were characterized by higher amounts of anthocyanins and other glycosylated and acetylated flavonoids, as well as phenolic acids; standard quality wines, on the other hand, presented stilbenoids and sulfonated catabolites of tryptophan and flavanols.

Grapevine and Wine Metabolomics-Based Guidelines for FAIR Data and Metadata Management.

In the era of big and omics data, good organization, management, and description of experimental data are crucial for achieving high-quality datasets. This, in turn, is essential for the export of robust results, to publish reliable papers, make data more easily available, and unlock the huge potential of data reuse. Lately, more and more journals now require authors to share data and metadata according to the FAIR (Findable, Accessible, Interoperable, Reusable) principles. This work aims to provide a step-by-step guideline for the FAIR data and metadata management specific to grapevine and wine science. In detail, the guidelines include recommendations for the organization of data and metadata regarding (i) meaningful information on experimental design and phenotyping, (ii) sample collection, (iii) sample preparation, (iv) chemotype analysis, (v) data analysis (vi) metabolite annotation, and (vii) basic ontologies. We hope that these guidelines will be helpful for the grapevine and wine metabolomics community and that it will benefit from the true potential of data usage in creating new knowledge being revealed.

H/D Exchange Processes in Flavonoids: Kinetics and Mechanistic Investigations.

Several classes of flavonoids, such as anthocyanins, flavonols, flavanols, and flavones, undergo a slow H/D exchange on aromatic ring A, leading to full deuteration at positions C(6) and C(8). Within the flavanol class, H-C(6) and H-C(8) of catechin and epicatechin are slowly exchanged in D2O to the corresponding deuterated analogues. Even quercetin, a relevant flavonol representative, shows the same behaviour in a D2O/DMSOd6 1:1 solution. Detailed kinetic measurements of these H/D exchange processes are here reported by exploiting the time-dependent changes of their peak areas in the 1H-NMR spectra taken at different temperatures. A unifying reaction mechanism is also proposed based on our detailed kinetic observations, even taking into account pH and solvent effects. Molecular modelling and QM calculations were also carried out to shed more light on several molecular details of the proposed mechanism.

Cluster Thinning and Vineyard Site Modulate the Metabolomic Profile of Ribolla Gialla Base and Sparkling Wines.

Depending on the vineyard location, cluster thinning (CT) may represent an effective tool to obtain the desired grape composition and wine quality. The effect of 20% cluster thinning on Ribolla Gialla (Vitis vinifera L.) sparkling wine aroma, lipid compounds, and aromatic amino acid (AAA) metabolites composition was studied for three consecutive seasons in two vineyards located in the Friuli Venezia Giulia region, Italy. In the examined sparkling wines, the vintage meteorological conditions exhibited significant influences on the metabolic profile of the samples. Data were normalized by season, and the impact of the CT treatment was evaluated for each vineyard site separately. Crop removal showed a limited positive impact on aroma compounds in sparkling wines from vineyards located in the valley. Concerning the AAA compounds, their concentration was higher in the vineyard at the foot of the hills. Cluster thinning resulted in a drop in concentration, reducing the risk of atypical aging. Despite minor differences according to targeted metabolome profiling, the sensory analysis confirmed the effects of the CT treatment in the valley floor vineyard. Reducing crop in this site, where the yield was higher, promoted a moderate improvement of Ribolla Gialla sparkling wine. In contrast, for wine produced in the vineyard at the foot of the hills, the sensory analysis indicated a preference for wines from the unthinned control samples. Overall, the study indicates that cluster thinning is a viticultural technique that could potentially improve the quality of Ribolla Gialla sparkling wines, but only in situations of excessive grape production.

The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols.

BACKGROUND: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of Wolffia globosa 'Mankai', a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial. METHODS: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet. RESULTS: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes. CONCLUSIONS: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis.

Diversity of Italian red wines: A study by enological parameters, color, and phenolic indices.

An extensive survey was conducted on 110 Italian monovarietal red wines from a single vintage to determine their standard compositional, color, and phenolic characteristics, analysing more than 35 parameters evaluated through methods commonly used in the wine industry. 'Primitivo' achieved the highest average alcohol strength (15.4% v/v) and dry extract values, while 'Cannonau' showed the lowest total acidity. 'Corvina' had the lowest phenolic content (1065 mg/L by Folin-Ciocalteu assay), remarkably different from the highest found in 'Sagrantino' (3578 mg/L), the latter being also the richest variety in both proanthocyanidins and vanillin-reactive flavanols. 'Teroldego' wines were the richest in both total and monomeric anthocyanins (702 and 315 mg/L, respectively), followed by 'Aglianico' and 'Raboso Piave', while 'Corvina', 'Nebbiolo', and 'Nerello Mascalese' were the poorest. 'Montepulciano' and 'Sangiovese' showed intermediate values for the majority of the parameters analyzed. A multivariate PCA-DA approach allowed achieving both a classification of the different wines as well as the discrimination of 'Sangiovese' wines produced in two regions (Emilia Romagna and Toscana) that returned a 42-66% success rate depending on the zone considered. Taking into account the number and diversity of the wines analyzed, a correlation study helped in better understanding the underlying relations between the most common and widespread analytical techniques for phenolic and color determinations.

Comparative Metabolite and Gene Expression Analyses in Combination With Gene Characterization Revealed the Patterns of Flavonoid Accumulation During Cistus creticus subsp. creticus Fruit Development.

Cistus creticus L. subsp. creticus (rockrose) is a shrub widespread in Greece and the Mediterranean basin and has been used in traditional medicine as herb tea for colds, for healing and digestive hitches, for the treatment of maladies, as perfumes, and for other purposes. Compounds from its flavonoid fraction have recently drawn attention due to antiviral action against influenza virus and HIV. Although several bioactive metabolites belonging to this group have been chemically characterized in the leaves, the genes involved in their biosynthesis in Cistus remain largely unknown. Flavonoid metabolism during C. creticus fruit development was studied by adopting comparative metabolomic and transcriptomic approaches. The present study highlights the fruit of C. creticus subsp. creticus as a rich source of flavonols, flavan-3-ols, and proanthocyanidins, all of which displayed a decreasing trend during fruit development. The majority of proanthocyanidins recorded in Cistus fruit are B-type procyanidins and prodelphinidins, while gallocatechin and catechin are the dominant flavan-3-ols. The expression patterns of biosynthetic genes and transcription factors were analyzed in flowers and throughout three fruit development stages. Flavonoid biosynthetic genes were developmentally regulated, showing a decrease in transcript levels during fruit maturation. A high degree of positive correlations between the content of targeted metabolites and the expression of biosynthetic genes indicated the transcriptional regulation of flavonoid biosynthesis during C. creticus fruit development. This is further supported by the high degree of significant positive correlations between the expression of biosynthetic genes and transcription factors. The results suggest that leucoanthocyanidin reductase predominates the biosynthetic pathway in the control of flavan-3-ol formation, which results in catechin and gallocatechin as two of the major building blocks for Cistus proanthocyanidins. Additionally, there is a decline in ethylene production rates during non-climacteric Cistus fruit maturation, which coincides with the downregulation of the majority of flavonoid- and ethylene-related biosynthetic genes and corresponding transcription factors as well as with the decline in flavonoid content. Finally, functional characterization of a Cistus flavonoid hydroxylase (F3'5'H) was performed for the first time.

Improving the Phloroglucinolysis Protocol and Characterization of Sagrantino Wines Proanthocyanidins.

Proanthocyanidins are key metabolites that explain wine sensorial character (bitterness and astringency) and red wine color changes during aging. Therefore, a fast and accurate method to evaluate the degree of polymerization and the structural composition of the polymeric proanthocyanidins is a crucial analytical tool. Phloroglucinolysis is the most used method for this analysis but, unfortunately, the phloroglucinol adducts of the monomeric flavan-3-ols are not commercially available, making the results less accurate. The aim of this work was the isolation by semi-preparative high performance liquid chromatography (HPLC) of these non-commercial compounds and their use for the development of an accurate UHPLC-MS/MS protocol. The purity of each adduct was established via quantitative 1H-nuclear magnetic resonance (NMR) measurements with 3-trimethylsilyl-propionic-d4 acid sodium salt as the calibration standard. The developed method was applied to evaluate the proanthocyanidins profile of Sagrantino di Montefalco wines in comparison to other well-known tannic wines. Commercial, 6-8 years old Sagrantino wines were demonstrated to be very rich in epicatechin type B procyanidins, to have low galloylation %, and to have a high mean degree of polymerization of the proanthocyanidins with respect to the other analyzed wines.

Exploring Olfactory-Oral Cross-Modal Interactions through Sensory and Chemical Characteristics of Italian Red Wines.

This work aimed at investigating red wine olfactory-oral cross-modal interactions, and at testing their impact on the correlations between sensory and chemical variables. Seventy-four Italian red whole wines (WWs) from 10 varieties, and corresponding deodorized wines (DWs), were evaluated by sensory descriptive assessment. Total phenols, proanthocyanidins, ethanol, reducing sugars, pH, titratable and volatile acidity were determined. PCA results highlighted different sensory features of the 10 wine types. ANOVAs (p < 0.05) showed that olfactory cues might play modulation effects on the perception of in-mouth sensations with 7 (harsh, unripe, dynamic, complex, surface smoothness, sweet, and bitter) out of 10 oral descriptors significantly affected by odours. Three weak but significant positive correlations (Pearson, p < 0.0001) were statistically found and supported in a cognitive dimension: spicy and complex; dehydrated fruits and drying; vegetal and unripe. In the absence of volatiles, correlation coefficients between sensory and chemical parameters mostly increased. Proanthocyanidins correlated well with drying and dynamic astringency, showing highest coefficients (r > 0.7) in absence of olfactory-oral interactions. Unripe astringency did not correlate with polyphenols supporting the idea that this sub-quality is a multisensory feeling greatly impacted by odorants. Results support the significance of cross-modal interactions during red wine tasting, confirming previous findings and adding new insights on astringency sub-qualities and their predictive parameters.

Modulating Wine Aromatic Amino Acid Catabolites by Using Torulaspora delbrueckii in Sequentially Inoculated Fermentations or Saccharomyces cerevisiae Alone.

Yeasts are the key microorganisms that transform grape juice into wine, and nitrogen is an essential nutrient able to affect yeast cell growth, fermentation kinetics and wine quality. In this work, we focused on the intra- and extracellular metabolomic changes of three aromatic amino acids (tryptophan, tyrosine, and phenylalanine) during alcoholic fermentation of two grape musts by two Saccharomyces cerevisiae strains and the sequential inoculation of Torulaspora delbrueckii with Saccharomyces cerevisiae. An UPLC-MS/MS method was used to monitor 33 metabolites, and 26 of them were detected in the extracellular samples and 8 were detected in the intracellular ones. The results indicate that the most intensive metabolomic changes occurred during the logarithm cellular growth phase and that pure S. cerevisiae fermentations produced higher amounts of N-acetyl derivatives of tryptophan and tyrosine and the off-odour molecule 2-aminoacetophenone. The sequentially inoculated fermentations showed a slower evolution and a higher production of metabolites linked to the well-known plant hormone indole acetic acid (auxin). Finally, the production of sulfonated tryptophol during must fermentation was confirmed, which also may explain the bitter taste of wines produced by Torulaspora delbrueckii co-fermentations, while sulfonated indole carboxylic acid was detected for the first time in such an experimental design.

Kinetic investigations of sulfite addition to flavanols.

Flavanols are an important class of natural products occurring in almost all plants, fruits and vegetables; they have a great influence on wine ageing potential, astringency, colour stability and biological activities. In wine, flavanols react with sulfur dioxide ([Formula: see text]), the most widely used preservative in oenology, leading to sulfonated products. Here we report a kinetic investigation, through LC-MS quantitative measurements carried out at different pH (3 and 4) and temperature values (23, 30, 40, 50 and [Formula: see text]), of the reaction products obtained by [Formula: see text] addition to both monomeric (epicatechin and catechin) and dimeric flavanols (procyanidin B2 and procyanidin B3). The results proved that: (a) the major sulfonation route that leads quickly and in good yields to monomeric 4[Formula: see text]-sulfonated derivatives passes through the acid-catalysed depolymerisation of proanthocyanidins; (b) monomeric flavanols lead to the same 4[Formula: see text]-sulfonated products, although in a considerably slower manner, and also to other sulfonated regioisomers; (c) the kinetic data in our hands, in particular the temperature dependence of the observed rates, suggest the involvement of two completely different reaction mechanisms for the [Formula: see text] addition to dimeric and monomeric flavanol substrates; (d) direct sulfonation of epicatechin is slightly faster than that of catechin.

Use of Untargeted Liquid Chromatography-Mass Spectrometry Metabolome To Discriminate Italian Monovarietal Red Wines, Produced in Their Different Terroirs.

The aim of this project was to register, in a liquid chromatography-mass spectrometry-based untargeted single-batch analysis, the metabolome of 11 single-cultivar, single-vintage Italian red wines (Aglianico, Cannonau, Corvina, Montepulciano, Nebbiolo, Nerello, Primitivo, Raboso, Sagrantino, Sangiovese, and Teroldego) from 12 regions across Italy, each one produced in their terroirs under ad hoc legal frameworks to guarantee their quality and origin. The data provided indications regarding the similarity between the cultivars and highlighted a rich list of putative biomarkers of origin wines (pBOWs) characterizing each individual cultivar-terroir combination, where Primitivo, Teroldego, and Nebbiolo had the maximum number of unique pBOWs. The pBOWs included anthocyanins (Teroldego), flavanols (Aglianico, Sangiovese, Nerello, and Nebbiolo), amino acids and N-containing metabolites (Primitivo), hydroxycinnamates (Cannonau), and flavonols (Sangiovese). The raw data generated in this study are publicly available and, therefore, accessible and reusable as a baseline data set for future investigations.

LC-MS untargeted approach showed that methyl jasmonate application on Vitis labrusca L. grapes increases phenolics at subtropical Brazilian regions.

INTRODUCTION: Vitis labrusca L. grapes are largely cultivated in Brazil, but the tropical climate negatively affects the phenols content, especially anthocyanin. According to the projections of the incoming climatic changes, the climate of several viticulture zone might change to tropical. Therefore, researches are focusing on increasing grape phenols content; with methyl jasmonate application (MeJa) is considered a good alternative. OBJECTIVES: The aim was to investigate with an untargeted approach the metabolic changes caused by the MeJa pre-harvest application on two Vitis labrusca L. cultivars grapes, both of them grown in two Brazilian regions. METHODS: Isabel Precoce and Concord grapes cultivated under subtropical climate, in the south and southeast of Brazil, received MeJa pre-harvest treatment. Grape metabolome was extracted and analyzed with a MS based metabolomics protocol by UPLC-HRMS-QTOF. RESULTS: Unsupervised data analysis revealed a clear separation between the two regions and the two cultivars, while supervised data analysis revealed biomarkers between the MeJa treatment group and the control group. Among the metabolites positively affected by MeJa were (a) flavonoids with a high degree of methylation at the B-ring (malvidin and peonidin derivatives and isorhamentin) for Isabel Precoce grapes; (b) glucosides of hydroxycinnamates, gallocatechin, epigallocatechin and cis-piceid for Concord grapes; and (c) hydroxycinnamates esters with tartaric acid, and procyanidins for the Southeast region grapes. CONCLUSION: These results suggest that MeJa can be used as elicitor to secondary metabolism in grapes grown even under subtropical climate, affecting phenolic biosynthesis.

Saccharomyces cerevisiae and Torulaspora delbrueckii Intra- and Extra-Cellular Aromatic Amino Acids Metabolism.

Tryptophan, phenylalanine, and tyrosine play an important role as nitrogen sources in yeast metabolism. They regulate biomass production and fermentation rate, and their catabolites contribute to wine health benefits and sensorial character through the yeast biotransformation of grape juice constitutes into biologically active and flavor-impacting components. A UHPLC-MS/MS method was applied to monitor 37 tryptophan/phenylalanine/tyrosine yeast metabolites both in extra- and intracellular extracts produced by the fermentation of two Saccharomyces cerevisiae strains and one Torulaspora delbrueckii. The results shed light on the intra- and extra-cellular metabolomic dynamics, by combining metabolic needs, stimuli, and signals. Among others, the results indicated (a) the production of 2-aminoacetophenone by yeasts, mainly by the two Saccharomyces cerevisiae; (b) the deactivation and/or detoxification of tryptophol via sulfonation reaction; and (c) the deacetylation of N-acetyl tryptophan ethyl ester and N-acetyl tyrosine ethyl ester by producing the corresponding ethyl esters.