Sensomics-assisted analysis unravels the formation of the Fungus Aroma of Fu Brick Tea.

Fu Brick Tea (FBT) is characterized by Fungus Aroma (FA), which determines the quality of FBT products. However, the aroma constituents and their interactive mechanism for FA remain unclear. In this study, the FBT sample with the optimal FA characteristics was selected from 29 FBTs. Then, 19 components with OAV ≥ 1 were identified as the odorants involved in the FA formation. The aroma recombination test suggested that the FA was potentially produced by the synergistic interplay among the 15 key odorants, including (E,E)-2,4-heptadienal, (E,E)-2,4-nonadienal, (E)-2-nonenal, (E,Z)-2,6-nonadienal, (E)-2-octenal, (E)-ß-ionone, 4-ketoisophorone, dihydroactinidiolide, (E)-ß-damascenone, 1-octen-3-ol, linalool, geraniol, heptanal, hexanal, and phenylacetaldehyde. And, the synergistic effects between them were preliminarily studied by aroma omissions, such as modulatory effects, masking effects, compensatory effects, and novelty effects, ultimately contributing to the FA. In all, this work helps us better understand the formation of the FA and provides a basis for the improvement of FBT production technology.

Linalool Reduces Virulence and Tolerance to Adverse Conditions of Listeria monocytogenes.

Listeria monocytogenes, a foodborne pathogen causing listeriosis, poses substantial societal, economic, and public health challenges due to its resistance, persistence, and biofilm formation in the food industry. Exploring subinhibitory concentrations of compounds to target virulence inhibition and increase susceptibility to adverse conditions presents a promising strategy to mitigate its impact of L. monocytogenes and unveils new potential applications. Thus, this study aims to explore the effect of linalool on virulence factors of L. monocytogenes and potential use in the reduction in its tolerance to stressful conditions. This action was analysed considering the use of two sub-inhibitory concentrations of linalool, 0.312 and 0.625 mg/mL. We found that even with the lowest tested concentrations, a 65% inhibition of violacein production by Chromobacterium violaceum, 55% inhibition in biofilm formation by L. monocytogenes and 62% reduction on haemolysis caused by this bacterium were observed. In addition to its impact on virulence factors, linalool diminished the tolerance to osmotic stress (up to 4.3 log reduction after 24 h with 12% NaCl), as well as to high (up to 3.8 log reduction after 15 min at 55 °C) and low temperatures (up to 4.6 log reduction after 84 days with 12% NaCl at 4 °C). Thus, this study paves the way to further investigation into the potential utilization of linalool to mitigate the threat posed by L. monocytogenes in the field of food safety and public health.

Floral scent changes in response to pollen removal are rare in buzz-pollinated Solanum.

MAIN CONCLUSION: One of seven Solanum taxa studied displayed associations between pollen presence and floral scent composition and volume, suggesting buzz-pollinated plants rarely use scent as an honest cue for foraging pollinators. Floral scent influences the recruitment, learning, and behaviour of floral visitors. Variation in floral scent can provide information on the amount of reward available or whether a flower has been visited recently and may be particularly important in species with visually concealed rewards. In many buzz-pollinated flowers, tubular anthers opening via small apical pores (poricidal anthers) visually conceal pollen and appear similar regardless of pollen quantity within the anther. We investigated whether pollen removal changes floral scent composition and emission rate in seven taxa of buzz-pollinated Solanum (Solanaceae). We found that pollen removal reduced both the overall emission of floral scent and the emission of specific compounds (linalool and farnesol) in S. lumholtzianum. Our findings suggest that in six out of seven buzz-pollinated taxa studied here, floral scent could not be used as a signal by visitors as it does not contain information on pollen availability.

Molybdenum Complexes Derived from 2-Hydroxy-5-nitrobenzaldehyde and Benzhydrazide as Potential Oxidation Catalysts and Semiconductors.

This study aimed to synthesize molybdenum complexes coordinated with an aroyl hydrazone-type ligand (H2L), which was generated through the condensation of 2-hydroxy-5-nitrobenzaldehyde with benzhydrazide. The synthesis yielded two types of mononuclear complexes, specifically [MoO2(L)(MeOH)] and [MoO2(L)(H2O)], as well as a bipyridine-bridged dinuclear complex, [(MoO2(L))2(4,4'-bpy)]. Those entities were thoroughly characterized using a suite of analytical techniques, including attenuated total reflectance infrared spectroscopy (IR-ATR), elemental analysis (EA), thermogravimetric analysis (TGA), and single-crystal X-ray diffraction (SCXRD). Additionally, solid-state impedance spectroscopy (SS-IS) was employed to investigate the electrical properties of these complexes. The mononuclear complexes were tested as catalysts in the epoxidation of cyclooctene and the oxidation of linalool. Among these, the water-coordinated mononuclear complex, [MoO2(L)(H2O)], demonstrated superior electrical and catalytic properties. A novel contribution of this research lies in establishing a correlation between the electrical properties, structural features, and the catalytic efficiency of the complexes, marking this work as one of the pioneering studies in this area for molybdenum coordination complexes, to the best of our knowledge.

Evaluation of the effect of active essential oil components added to pickled-based marinade on beef stored under vacuum packaging: Insight into physicochemical and microbiological quality.

This research aimed to evaluate the effects of the addition of active essential oil components (linalool and/or eugenol) to a pickle-based marinade on controlling spoilage and extending the shelf life of fresh beef stored under vacuum packaging at 4 °C. Linalool and eugenol were used either separately at a concentration of 0.2 % (w/w) or together (1:1 ratio) to preserve marinated beef under vacuum packaging for 15 days. Samples were assessed for pH, color, texture, oxidative degradation, and microbiological parameters. All marinades exhibited significantly lower TBARS values than the control sample. The addition of linalool or eugenol to the marinate showed a significant antibacterial effect on total aerobic mesophilic bacteria (TAMB), lactic acid bacteria (LAB), Pseudomonas spp., and total coliform, and the reductions in microbial counts are as follows: TAMB: 1.563 log CFU/g and 1.46 log CFU/g; Pseudomonas spp.: 1.303 log CFU/g and 1.08 log CFU/g; LAB: 0.323 log CFU/g and 0.357 log CFU/g. Marinated beef with linalool and/or eugenol was found to be effective against the growth of yeast and mold. The use of eugenol presented the most effective inhibition activity against yeast and mold by reducing the number of yeast and molds to an uncountable level on the 12th and 15th days of storage. Physicochemical analysis also showed that the addition of active essential oils to marinade did not cause any undesirable effects on the color and texture properties of beef samples. Therefore, the findings revealed that eugenol and linalool could be suitable alternatives for beef marination.

Reducing Temperature of Fused Deposition Modelling 3D Printing for Linalool Fast Dissolving Oral Films by Increasing Printer Nozzle Diameter.

Oral thrush and throat infections can occur in a wide range of patients. Treatments are available; however, resistance to drugs is a major problem for treating oral and throat infections. Three-dimensional printing (3DP) of fast dissolving oral films (FDFs) of linalool oil may provide an alternative solution. Linalool oil FDFs were printed by fused deposition modelling across 1-18 % w/w linalool content range with nozzle diameters of 0.4 or 1 mm at the temperature range of 150 °C-185 °C. The FDFs were evaluated for physicochemical and mechanical properties. Increasing the printer nozzle diameter to 1 mm allowed reducing the printing temperature from 185 °C to 150 °C; consequently, more linalool was quantified in the films with improved content uniformity. The higher linalool content in the films increased the film disintegration time and mechanical strength. FDFs containing 10% w/w linalool showed clear antifungal activity against Candida albicans. Raman spectroscopy suggested linalool separation from excipients at higher temperature printing. Viscoelastic measurements indicated that to achieve printing; the elastic modulus of molten filament needed to be higher than the loss modulus at low angular frequencies. In conclusion, increasing the printing nozzle diameter may avoid loss of the active ingredient by reducing the temperature of the 3DP process.

Characterization of volatile compounds from healthy and citrus black spot-infected Valencia orange juice and essential oil by using gas chromatography-mass spectrometry.

Citrus black spot (Phyllosticta citricarpa, CBS) is an important fungal disease that causes rind blemishes and affects quality of citrus fruits. The response of citrus to CBS in terms of volatiles was evaluated using molecular sensory science approaches. Fifty and twenty-one volatiles were identified in the orange juice and essential oil samples, respectively, via gas chromatography-mass spectrometry (GC-MS). The total volatile content in the samples increased after CBS infection, especially in the severe-infection group (SEG) juice and moderate-infection group (MOG) essential oil, which reached the highest levels. CBS enhanced floral, fruity, and off-flavor aromas and decreased the green aroma in citrus juice. Citrusy, floral, and green aromas increased in the CBS-infected essential oil. Six/five potential markers were screened in citrus juice/essential oil, respectively using the orthogonal partial least-square discriminant analysis (OPLS-DA) model. The changes in aroma profile and the difference in infection levels in citrus were attributed to these odorants.

Unraveling the Enantiomeric Distribution of Glycosidically Bound Linalool in Teas (Camellia sinensis) and Their Acidolysis Characteristics and Pyrolysis Mechanism.

Glycosidically bound linalool plays important roles in the formation of excellent tea flavor, while their enantiomeric distribution in teas and the actual transformations with free linalool are still unclear. In this study, a novel chiral ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry approach to directly analyze linalyl-ß-primeveroside and linalyl-ß-d-glucopyranoside enantiomers in teas was established and then applied in 30 tea samples. A close transformation relationship existed between the two states of linalool for their consistent dominant configurations (most S-form) and corresponding distribution trend in most teas (r up to 0.81). The acidolysis characterization indicated that free linalool might be slowly released from linalyl-ß-primeveroside with stable enantiomeric ratios during long-term withering of white tea in a weakly acidic environment, along with other isomerized products, e.g., geraniol, nerol, α-terpineol, etc. Furthermore, a novel online thermal desorption-gas chromatography-mass spectrometry approach was established to simulate the pyrolysis releasing of linalyl-ß-primeveroside during tea processing. Interestingly, free linalool was not the selected pyrolysis product of linalyl-ß-primeveroside but rather trans/cis-2,6-dimethyl-2,6-octadiene during the high-fire roasting or baking step of oolong and green teas. The identification of above high-fire chemical marks presented great potential to scientifically evaluate the proper thermal conditions in the practical production of tea.

Insights into the antibacterial effectiveness of linalool against Shigella flexneri on pork surface: Changes in bacterial growth and pork quality.

Shigella flexneri has the ability to contaminate pork and cause foodborne diseases. This study aimed to examine the effectiveness of linalool (a natural preservative) against S. flexneri and explore its potential application in contaminated pork. The results showed that linalool was capable of damaging the cell membrane and binding to the DNA of S. flexneri, and inhibiting biofilm formation and disrupting mature biofilms. The antibacterial effectiveness of linalool on the surface of pork was further demonstrated by analyzing the physicochemical properties of the pork (i.e., weight loss rate, pH value, color index, and TVB-N value) and its protein profiles. Linalool did not completely kill S. flexneri in pork at minimum bactericidal concentration (MBC) concentration and its antibacterial effect of linalool was stronger during the initial stage of storage. During storage, linalool influenced the abundance of specific proteins in the pork, particularly those involved in pathways related to fat metabolism. These findings offer novel insights into the antibacterial efficacy of linalool and its underlying mechanism in pork.

Therapeutic potential of the linalool against cadmium-induced testicular tissue damage.

Cadmium (Cd) is a heavy metal that has harmful effects and is one of the contaminants found in the environment. Cd exposure causes important pathophysiological processes, such as reproductive toxicity. Linalool (Lnl) is a monoterpene, a component of essential oils known to be produced synthetically. Additionally, Lnl has many important beneficial effects, such as anti-inflammatory and antioxidant effects. The objective of this study is to determine whether Lnl has a healing impact in opposition to testicular tissue damage due to Cd exposure. In the study, 28 male rats were divided at random into four equal groups (n = 7). No treatment was applied to the control group. CdCl2 was applied intraperitoneally to the Cd group at a dose of 3 mg/kg for the first 7 days of the trial. For the Cd + Lnl group, 3 mg/kg CdCl2 was applied intraperitoneally for the first 7 days of the trial, and 100 mg/kg/day Lnl was applied. Upon completion of all applications, the rats were sacrificed and blood samples and testicular tissue were taken. Cd exposure caused histopathological changes, oxidative stress, inflammation, and an increase in apoptotic cells in testicular tissue. However, Cd altered endocrine hormones in the hypothalamic-pituitary-gonad axis. However, Lnl application against Cd exposure was able to regulate the negativity caused by Cd in both testicular tissue and endocrine hormone levels. In conclusion, Lnl may be a potential therapeutic strategy against Cd-induced reproductive toxicity. We believe that Lnl has a high potential for further studies to determine its detailed mechanisms of action and cellular signaling pathways.

Polymer Beads Increase Field Responses to Host Attractants in the Dengue Vector Aedes aegypti.

This study investigates the efficacy of three different olfactory cues - cyclohexanone, linalool oxide (LO), and 6-methyl-5-heptan-2-one (sulcatone) - in attracting Aedes aegypti, the primary vector of dengue, using BG sentinel traps in a dengue-endemic area (urban Ukunda) in coastal Kenya. Two experiments were conducted. Experiment 1 compared solid formulations of the compounds in polymer beads against liquid formulations with hexane as the solvent. CO2-baited traps served as controls. In Experiment 2, traps were baited with each compound in the polymer beads, commercial BG-Lure, and CO2. Our results indicate that CO2-baited traps recorded the greatest Ae. aegypti captures in both Experiment 1 and 2, whereas trap captures with polymer beads and solvent-based treatments were comparable. In experiment 2, polymer bead-based treatments yielded significantly greater female captures, each recording ~ 2-fold more captures than traps baited with the BG-Lure. There was no significant difference, however, between the treatments. Female Ae. aegypti captured in CO2-baited traps were mainly unfed (91%), with fewer gravid mosquitoes (6.4%) compared to traps with test compounds (range; 12.7-21.1%). Male captures were lower in LO and BG-Lure baited traps compared to other treatments. Gravimetric analysis showed LO had a slower release rate compared to other compounds. The findings suggest that host-associated compounds loaded on polymer beads are more effective in trapping Ae. aegypti than commercial BG-Lure and reveal sex-specific differences in mosquito responses. These results have implications for mosquito surveillance and control programs, highlighting the potential for selective trapping strategies.

Linalool, a Fragrance Compound in Plants, Protects Dopaminergic Neurons and Improves Motor Function and Skeletal Muscle Strength in Experimental Models of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.

Ability of Selected Monoterpenes to Reduce Fe(III) Ions Being Pro-Neurodegenerative Factors: Tests Based on a FRAP Reaction Extended to 48 Hours.

Monoterpenes are secondary plant metabolites, and such volatile compounds have antioxidant, antibacterial, antiviral, and enzyme inhibitory properties. These compounds are also able to reduce the potentially pro-neurodegenerative trace metal ions that can be sources of free radicals. One basic method used to evaluate the ability of chemical compounds to reduce Fe(III) is FRAP. To date, most studies based on a FRAP assay were performed within several dozen minutes. However, taking into account the diversity of compounds, it is justified to observe their activity over a much longer period of time. The present study aimed to observe the activity of isopulegol, γ-terpinene, α-terpinene, linalool, carvone, citral, and α-phellandrene over a 48 h period. Our study indicates that the lengthened reaction period enhanced activity from several dozen to several hundred percent. The obtained results also revealed an explicit high correlation of the increase in the activity of compounds with the increase in monoterpene concentration. Due to the hydrophobic character of monoterpenes, the FRAP method was modified by the addition of Tween 20. The highest activity was obtained for α-terpinene and γ-terpinene.

Effects of linalool on postoperative peritoneal adhesions in rats.

The current study examines the effects of linalool in preventing postoperative abdominal adhesions. Twenty male Wistar rats were randomly divided into four groups. (1) Sham: in this group, the abdomen was approached, and without any manipulations, it was sutured. (2) Control: rats in this group underwent a surgical procedure to induce adhesions. This involved making three incisions on the right abdominal side and removing a 1×1-cm piece of the peritoneum on the left abdominal side. (3) Treatment groups: these groups underwent the same surgical procedure as the control group to induce adhesions. Animals in these groups received linalool orally with doses of 50 and 100 mg/kg, respectively, for a period of 14 days. Moreover, rats in the sham and control groups received normal saline via gavage for 14 days. The evaluation of TNF-α, TGF-ß, VEGF, and caspase 3 was performed using western blot and IHC methods. Furthermore, oxidative stress biomarkers such as MDA, TAC, GSH, and NO were assessed in the peritoneal adhesion tissue. The findings revealed that linalool significantly reduced peritoneal adhesions by reducing TNF-α, TGF-ß, VEGF, and caspase 3 levels. Moreover, MDA concentration was significantly decreased, while NO, TAC, and GSH levels were notably increased. Overall, linalool was effective in preventing adhesion formation and reduced inflammation, angiogenesis, apoptosis, and oxidative stress. Therefore, linalool as a potent antioxidant is suggested for reducing postoperative adhesions in rats.

Circabidian rhythm of sex pheromone reception in a scarab beetle.

Animals have endogenous clocks that regulate their behavior and physiology. These clocks rely on environmental cues (time givers) that appear approximately every 24 h due to the Earth's rotation; thus, most insects exhibit a circadian rhythm. One notable exception is the scarab beetle, Holotrichia parallela, a severe agricultural pest in China, Japan, South Korea, and India. Females emerge from the soil every other night, reach the canopy of host plants, evert an abdominal gland, and release a pheromone bouquet comprising l-isoleucine methyl ester (LIME) and l-linalool. To determine whether this circa'bi'dian rhythm affects the olfactory system, we aimed to identify H. parallela sex pheromone receptor(s) and study their expression patterns. We cloned 14 odorant receptors (ORs) and attempted de-orphanizing them in the Xenopus oocyte recording system. HparOR14 gave robust responses to LIME and smaller responses to l-linalool. Structural modeling, tissue expression profile, and RNAi treatment followed by physiological and behavioral studies support that HparOR14 is a sex pheromone receptor-the first of its kind discovered in Coleoptera. Examination of the HparOR14 transcript levels throughout the adult's life showed that on sexually active days, gene expression was significantly higher in the scotophase than in the photophase. Additionally, the HparOR14 expression profile showed a circabidian rhythm synchronized with the previously identified pattern of sex pheromone emission. 48 h of electroantennogram recordings showed that responses to LIME were abolished on non-calling nights. In contrast, responses to the green leaf volatile (Z)-3-henexyl acetate remained almost constant throughout the recording period.

Alleviating effect of lavender (Lavandula angustifolia) and its major components on postherpetic pain: a randomized blinded controlled trial.

BACKGROUND: Postherpetic neuralgia (PHN) causes severe pain which can lead to decreased quality-of-life. This study aimed to evaluate the effects of inhalation of lavender (Lavandula angustifolia) oil and its major components (linalool and linalyl acetate) on the pain in patients with PHN. METHODS: This study was performed at an outpatient clinic. Sixty-four patients with postherpetic neuralgia were randomly allocated to a control group (almond oil) or one of three experimental groups (lavender oil, linalool, or linalyl acetate diluted in almond oil at concentration of 1% v/v), and the participants inhaled the aroma by natural breathing. Quality, severity, and intensity of pain were measured before and after the intervention. RESULTS: Six patients discontinued the intervention for personal reasons; hence, data from 58 patients were analyzed (control group, n = 14; 1% lavender oil group, n = 15; 1% linalool, n = 15; 1% linalyl acetate, n = 14). Reduction in sensory pain was greater in the 1% lavender oil group, 1% linalool group, and 1% linalyl acetate group than in the control group (all P < 0.001). Reduction in affective pain was greater in the 1% lavender group (P < 0.001) and the 1% linalool group (P = 0.007) than in the control group. Decreases in pain severity and intensity were significantly greater in all three intervention groups than in the control group. CONCLUSIONS: Inhalation of lavender oil and its major volatile components effectively reduced the quality, severity, and intensity of postherpetic pain, suggesting that lavender oil, linalool, and linalyl acetate may each be an effective intervention for reducing pain in patients with postherpetic neuralgia. TRIAL REGISTRATION: This study was retrospectively registered on the Clinical Research Information Service. REGISTRATION NUMBER: KCT0007772, first registration 06/10/2022.

Monoterpene linalool restrains gentamicin-mediated acute kidney injury in rats by subsiding oxidative stress, apoptosis, and the NF-κB/iNOS/TNF-α/IL-1ß pathway and regulating TGF-ß.

The clinical use of gentamicin (GM) is restricted by its nephrotoxic effects. This study aimed for the first time to elucidate the ameliorative effects of the monoterpene linalool (Lin) against GM-mediated acute kidney injury in rats. A total of thirty-two rats were subdivided into four equal groups: control (saline), Lin (100 mg/kg/day), GM (100 mg/kg/day), and GM + Lin (100 and 100 mg/kg/day). Lin and GM were intraperitoneally administered for 12 days. Our results illustrated that Lin ameliorated GM-mediated renal histopathological abnormalities and reduced serum urea and creatinine levels in rats exposed to GM. Lin treatment mitigated oxidative stress in nephrotoxic animals as manifested by reducing serum and renal levels of malondialdehyde and increasing the activities of serum and renal glutathione peroxidase and renal catalase. Moreover, Lin markedly inhibited GM-triggered inflammation by downregulating NF-κB, iNOS, TNF-α, and IL-1ß and reducing renal myeloperoxidase activity and nitric oxide levels. Interestingly, Lin repressed GM-induced apoptosis, as reflected by a marked downregulation of Bax and caspase-3 expression, concurrent with the upregulation of Bcl2 expression. Finally, Lin administration led to a significant downregulation of TGF-ß expression in nephrotoxic animals. In summary, Lin ameliorated GM-mediated nephrotoxicity in rats, at least through its antioxidant, anti-inflammatory, and anti-apoptotic activities and by modulating TGF-ß.

Boosting Geranyl Diphosphate Synthesis for Linalool Production in Engineered Yarrowia lipolytica.

Linalool is a pleasant-smelling monoterpenoid widely found in the essential oils of most flowers. Due to its biologically active properties, linalool has considerable commercial potential, especially in the food and perfume industries. In this study, the oleaginous yeast Yarrowia lipolytica was successfully engineered to produce linalool de novo. The (S)-linalool synthase (LIS) gene from Actinidia argute was overexpressed to convert geranyl diphosphate (GPP) into linalool. Flux was diverted from farnesyl diphosphate (FPP) synthesis to GPP by introducing a mutated copy of the native ERG20F88W-N119W gene, and CrGPPS gene from Catharanthus roseus on its own and as part of a fusion with LIS. Disruption of native diacylglycerol kinase enzyme, DGK1, by oligo-mediated CRISPR-Cas9 inactivation further increased linalool production. The resulting strain accumulated 109.6 mg/L of linalool during cultivation in shake flasks with sucrose as a carbon source. CrGPPS expression in Yarrowia lipolytica increased linalool accumulation more efficiently than the ERG20F88W-N119W expression, suggesting that the increase in linalool production was predominantly influenced by the level of GPP precursor supply.

Development of Corynebacterium glutamicum as a monoterpene production platform.

Monoterpenes are commonly known for their role in the flavors and fragrances industry and are also gaining attention for other uses like insect repellant and as potential renewable fuels for aviation. Corynebacterium glutamicum, a Generally Recognized as Safe microbe, has been a choice organism in industry for the annual million ton-scale bioproduction of amino acids for more than 50 years; however, efforts to produce monoterpenes in C. glutamicum have remained relatively limited. In this study, we report a further expansion of the C. glutamicum biosynthetic repertoire through the development and optimization of a mevalonate-based monoterpene platform. In the course of our plasmid design iterations, we increased flux through the mevalonate-based bypass pathway, measuring isoprenol production as a proxy for monoterpene precursor abundance and demonstrating the highest reported titers in C. glutamicum to date at 1504.6 mg/L. Our designs also evaluated the effects of backbone, promoter, and GPP synthase homolog origin on monoterpene product titers. Monoterpene production was further improved by disrupting competing pathways for isoprenoid precursor supply and by implementing a biphasic production system to prevent volatilization. With this platform, we achieved 321.1 mg/L of geranoids, 723.6 mg/L of 1,8-cineole, and 227.8 mg/L of linalool. Furthermore, we determined that C. glutamicum first oxidizes geraniol through an aldehyde intermediate before it is asymmetrically reduced to citronellol. Additionally, we demonstrate that the aldehyde reductase, AdhC, possesses additional substrate promiscuity for acyclic monoterpene aldehydes.

Critical assessment of the endocrine potential of Linalool and Linalyl acetate: proactive testing strategy assessing estrogenic and androgenic activity of Lavender oil main components.

The acyclic linear monoterpenes Linalool (Lin) and Linalyl acetate (LinAc) occur in nature as major constituents of various essential oils such as lavender oils. A potential endocrine activity of these compounds was discussed in literature including premature thelarche and prepubertal gynecomastia due to lavender product use. This study aims to follow-up on these critical findings reported by testing Lin and LinAc in several studies in line with current guidance and regulatory framework. No relevant anti-/ER and AR-mediated activity was observed in recombinant yeast cell-based screening tests and guideline reporter gene in vitro assays in mammalian cells. Findings in the screening test suggested an anti-androgenic activity, which could not be confirmed in the respective mammalian cell guideline assay. Mechanistic guideline in vivo studies (Uterotrophic and Hershberger assays) with Lin did not show significant dose related changes in estrogen or androgen sensitive organ weights and a guideline reproductive toxicity screening study did not reveal evident effects on sex steroid hormone sensitive organ weights, associated histopathological findings and altered sperm parameters. Estrous cycling and mating/fertility indices were not affected and no evident Lin-related steroid hormone dependent effects were found in the offspring. Overall, the initial concerns from literature were not confirmed. Findings in the yeast screening test were aberrant from follow-up guideline in vitro and in vivo studies, which underlines the need to apply careful interpretation of single in vitro test results to support a respective line of evidence and to establish a biologically plausible link to an adverse outcome.