Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms.

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.

Synthesis and Characterization of Organic Peroxides from Monoterpene-Derived Criegee Intermediates in Secondary Organic Aerosol.

Ozonolysis of alkenes is known to produce reactive intermediates─stabilized Criegee intermediates (SCIs), and their subsequent bimolecular reactions with various carboxylic acids can form α-acyloxyalkyl hydroperoxides (AAHPs), which is considered a major class of organic peroxides in secondary organic aerosol (SOA). Despite their atmospheric and health importance, the molecular-level identification of organic peroxides in atmospheric aerosols is highly challenging, preventing further assessment of their environmental fate. Here, we synthesize 20 atmospherically relevant AAHPs through liquid-phase ozonolysis, in which two types of monoterpene-derived SCIs from either α-pinene or 3-carene are scavenged by 10 different carboxylic acids to form AAHPs with diverse structures. These AAHPs are identified individually by liquid chromatography coupled with high-resolution mass spectrometry. AAHPs were previously thought to decompose quickly in an aqueous environment such as cloud droplets, but we demonstrate here that AAHPs hydrolysis rates are highly compound-dependent with rate constants differing by 2 orders of magnitude. In contrast, the aqueous-phase formation rate constants between SCI and various carboxylic acids vary only within a factor of 2-3. Finally, we identified two of the 20 synthesized AAHPs in α-pinene SOA and two in 3-carene SOA, contributing ∼0.3% to the total SOA mass. Our results improve the current molecular-level understanding of organic peroxides and are useful for a more accurate assessment of their environmental fate and health impact.

Efficient Capture of Cannabis Terpenes in Olive Oil during Microwave-Assisted Cannabinoid Decarboxylation.

The development of selective extraction protocols for Cannabis-inflorescence constituents is still a significant challenge. The characteristic Cannabis fragrance can be mainly ascribed to monoterpenes, sesquiterpenes and oxygenated terpenoids. This work investigates the entrapment of Cannabis terpenes in olive oil from inflorescences via stripping under mild vacuum during the rapid microwave-assisted decarboxylation of cannabinoids (MW, 120 °C, 30 min) and after subsequent extraction of cannabinoids (60 and 100 °C). The profiles of the volatiles collected in the oil samples before and after the extraction step were evaluated using static headspace solid-phase microextraction (HS-SPME), followed by gas chromatography coupled to mass spectrometry (GC-MS). Between the three fractions obtained, the first shows the highest volatile content (~37,400 mg/kg oil), with α-pinene, ß-pinene, ß-myrcene, limonene and trans-ß-caryophyllene as the main components. The MW-assisted extraction at 60 and 100 °C of inflorescences using the collected oil fractions allowed an increase of 70% and 86% of total terpene content, respectively. Considering the initial terpene amount of 91,324.7 ± 2774.4 mg/kg dry inflorescences, the percentage of recovery after decarboxylation was close to 58% (mainly monoterpenes), while it reached nearly 100% (including sesquiterpenes) after extraction. The selective and efficient extraction of volatile compounds, while avoiding direct contact between the matrix and extraction solvents, paves the way for specific applications in various aromatic plants. In this context, aromatized extracts can be employed to create innovative Cannabis-based products within the hemp processing industry, as well as in perfumery, cosmetics, dietary supplements, food, and the pharmaceutical industry.

Nitrate Radicals Suppress Biogenic New Particle Formation from Monoterpene Oxidation.

Highly oxygenated organic molecules (HOMs) are a major source of new particles that affect the Earth's climate. HOM production from the oxidation of volatile organic compounds (VOCs) occurs during both the day and night and can lead to new particle formation (NPF). However, NPF involving organic vapors has been reported much more often during the daytime than during nighttime. Here, we show that the nitrate radicals (NO3), which arise predominantly at night, inhibit NPF during the oxidation of monoterpenes based on three lines of observational evidence: NPF experiments in the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN (European Organization for Nuclear Research), radical chemistry experiments using an oxidation flow reactor, and field observations in a wetland that occasionally exhibits nocturnal NPF. Nitrooxy-peroxy radicals formed from NO3 chemistry suppress the production of ultralow-volatility organic compounds (ULVOCs) responsible for biogenic NPF, which are covalently bound peroxy radical (RO2) dimer association products. The ULVOC yield of α-pinene in the presence of NO3 is one-fifth of that resulting from ozone chemistry alone. Even trace amounts of NO3 radicals, at sub-parts per trillion level, suppress the NPF rate by a factor of 4. Ambient observations further confirm that when NO3 chemistry is involved, monoterpene NPF is completely turned off. Our results explain the frequent absence of nocturnal biogenic NPF in monoterpene (α-pinene)-rich environments.

Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases.

The interconversion of monoterpenes is facilitated by a complex network of carbocation rearrangement pathways. Controlling these isomerization pathways is challenging when using common Brønsted and Lewis acid catalysts, which often produce product mixtures that are difficult to separate. In contrast, natural monoterpene cyclases exhibit high control over the carbocation rearrangement reactions but are reliant on phosphorylated substrates. In this study, we present engineered squalene-hopene cyclases from Alicyclobacillus acidocaldarius (AacSHC) that catalyze the challenging isomerization of monoterpenes with unprecedented precision. Starting from a promiscuous isomerization of (+)-ß-pinene, we first demonstrate noticeable shifts in the product distribution solely by introducing single point mutations. Furthermore, we showcase the tuneable cation steering by enhancing (+)-borneol selectivity from 1 % to >90 % (>99 % de) aided by iterative saturation mutagenesis. Our combined experimental and computational data suggest that the reorganization of key aromatic residues leads to the restructuring of the water network that facilitates the selective termination of the secondary isobornyl cation. This work expands our mechanistic understanding of carbocation rearrangements and sets the stage for target-oriented skeletal reorganization of broadly abundant terpenes.

Tautomeric cinnamoylphloroglucinol-monoterpene adducts from Cleistocalyx operculatus and their antiviral activities.

Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1-3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1-3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4-C-1' linkage between 2,2,4-trimethyl-cinnamyl-ß-triketone and modified linear monoterpenoid motifs. Notably, compounds 1-3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV).

Study of Glycosidically Bound Volatile Precursors as Variety Markers to Reveal Not-Allowed Practices in White Wines Winemaking.

Liquid chromatography/high-resolution mass spectrometry (LC/HRMS) can provide identification of grape metabolites which are variety markers. White grapes are poorer in polyphenolics, and the main secondary metabolites which contribute the sensorial characteristics of wines are the glycosidically bound volatile precursors and their aglycones. The profiles of three white grape juices (Pinot grigio, Garganega, and Trebbiano) were characterized by LC/HRMS, and 70 signals of putative glycosidic terpenols, norisoprenoids, and benzenoids were identified. Four signals found only in Pinot grigio corresponded to a norisoprenoid hexose-hexose, 3-oxo-α-ionol (or 3-hydroxy-ß-damascone) rhamnosyl-hexoside, monoterpene-diol hexosyl-pentosyl-hexoside, and hexose-norisoprenoid; three signals were found only in Garganega (putative isopropyl alcohol pentosyl-hexoside, phenylethanol rhamnosyl-hexoside, and norisoprenoid hexose-hexose isomers), and a monoterpenol pentosyl-hexoside isomer only in Trebbiano. These variety markers were then investigated in juice blends of the three varieties. This approach can be used to develop control methods to reveal not-allowed grape varieties and practices in white wines winemaking.

Antifungal effects of carvacrol, the main volatile compound in Origanum vulgare L. essential oil, against Aspergillus flavus in postharvest wheat.

Plant volatile organic compounds (VOCs) with antimicrobial activity could potentially be extremely useful fumigants to prevent and control the fungal decay of agricultural products postharvest. In this study, antifungal effects of volatile compounds in essential oils extracted from Origanum vulgare L. against Aspergillus flavus growth were investigated using transcriptomic and biochemical analyses. Carvacrol was identified as the major volatile constituent of the Origanum vulgare L. essential oil, accounting for 66.01 % of the total content. The minimum inhibitory concentrations of carvacrol were 0.071 and 0.18 µL/mL in gas-phase fumigation and liquid contact, respectively. Fumigation with 0.60 µL/mL of carvacrol could completely inhibit A. flavus proliferation in wheat grains with 20 % moisture, showing its potential as a biofumigant. Scanning electron microscopy revealed that carvacrol treatment caused morphological deformation of A. flavus mycelia, and the resulting increased electrolyte leakage indicates damage to the plasma membrane. Confocal laser scanning microscopy confirmed that the carvacrol treatment caused a decrease in mitochondrial membrane potential, reactive oxygen species accumulation, and DNA damage. Transcriptome analysis revealed that differentially expressed genes were mainly associated with fatty acid degradation, autophagy, peroxisomes, the tricarboxylic acid cycle, oxidative phosphorylation, and DNA replication in A. flavus mycelia exposed to carvacrol. Biochemical analyses of hydrogen peroxide and superoxide anion content, and catalase, superoxide dismutase, and glutathione S-transferase activities showed that carvacrol induced oxidative stress in A. flavus, which agreed with the transcriptome results. In summary, this study provides an experimental basis for the use of carvacrol as a promising biofumigant for the prevention of A. flavus contamination during postharvest grain storage.

Biosynthesis of Haloterpenoids in Red Algae via Microbial-like Type I Terpene Synthases.

Red algae or seaweeds produce highly distinctive halogenated terpenoid compounds, including the pentabromochlorinated monoterpene halomon that was once heralded as a promising anticancer agent. The first dedicated step in the biosynthesis of these natural product molecules is expected to be catalyzed by terpene synthase (TS) enzymes. Recent work has demonstrated an emerging class of type I TSs in red algal terpene biosynthesis. However, only one such enzyme from a notoriously haloterpenoid-producing red alga (Laurencia pacifica) has been functionally characterized and the product structure is not related to halogenated terpenoids. Herein, we report 10 new type I TSs from the red algae Portieria hornemannii, Plocamium pacificum, L. pacifica, and Laurencia subopposita that produce a diversity of halogenated mono- and sesquiterpenes. We used a combination of genome sequencing, terpenoid metabolomics, in vitro biochemistry, and bioinformatics to establish red algal TSs in all four species, including those associated with the selective production of key halogenated terpene precursors myrcene, trans-ß-ocimene, and germacrene D-4-ol. These results expand on a small but growing number of characterized red algal TSs and offer insight into the biosynthesis of iconic halogenated algal compounds that are not without precedence elsewhere in biology.

Thermal reaction products and formation pathways of two monoterpenes under in situ thermal desorption conditions that mimic vaping coil temperatures.

Vaping has become more popular and different brands and types of vaping devices have rapidly emerged. However, little is known about the potential health risks of human inhalation exposures to the volatile chemicals in the vapour, which includes both directly vaporised components of vaping liquid and their reaction products formed during vaping processes. This study investigated reaction products of two monoterpenes (α-pinene and terpinolene) that are used as flavouring agents in vaping liquids with a focus on the identification of reaction products and their formation pathways. The thermal desorption was conducted under an in situ condition that is in the range of heating coil temperature in vaping by thermally desorbing the chemicals at a temperature range of 100-300 °C. Additional clean air was introduced during the thermal desorption. 36 and 29 reaction products were identified from α-pinene and terpinolene, respectively, at a relative concentration of 0.01% and greater in the desorbed mixture. 3-Carene was the dominant reaction product of α-pinene, while reaction products of terpinolene was dominated by p-isopropenyltoluene. Several reaction pathways including ring opening, allylic oxidation, cyclo-etherification, Wagner-Meerwein rearrangement, epoxidation, cleavage and removal of partial structure, and dehydration were involved in the formation of various reaction products. These pathways and resulting relative concentrations of residual parent compound and reaction products were influenced by both temperature and amount of air present during thermal desorption. The study results demonstrate possible existence of reaction products from thermally labile chemicals like monoterpenes in vaping aerosols and can help inform policies regulating vaping devices and products to protect public health.

Composition and Anti-Acetylcholinesterase Properties of the Essential Oil of the Ecuadorian Endemic Species Eugenia valvata McVaugh.

Alzheimer's disease is a global health problem due to the scarcity of acetylcholinesterase inhibitors, the basis for symptomatic treatment of this disease; this requires new approaches to drug discovery. In this study, we investigated the chemical composition and anticholinesterase activity of Eugenia valvata McVaugt (Myrtaceae) collected in southern Ecuador, which was obtained as an essential oil (EO) with a yield of 0.124 ± 0.03% (w/w); as a result of the chemical composition analysis, a total of 58 organic compounds were identified-representing 95.91% of the total volatile compounds-using a stationary phase based on 5% phenyl-methylpolysiloxane, as analyzed via gas chromatography coupled to mass spectrometry (GC-MS) and flame ionization detection (GC-FID). The main groups were hydrocarbon sesquiterpenes (37.43%), oxygenated sesquiterpenes (31.08%), hydrocarbon monoterpenes (24.14%), oxygenated monoterpenes (0.20%), and other compounds (3.058%). Samples were characterized by the following compounds: α-pinene (22.70%), α-humulene (17.20%), (E)-caryophyllene (6.02%), citronellyl pentanoate (5.76%), 7-epi-α-eudesmol (4.34%) and 5-iso-cedranol (3.64%); this research was complemented with an enantioselective analysis carried out using 2,3-diethyl-6-tert-butyldimethylsilyl-ß-cyclodextrin as a stationary phase chiral selector. As a result, α-pinene, limonene, and α-cadinene enantiomers were identified; finally, in the search for new active principles, the EO reported strong anticholinesterase activity with an IC50 of 53.08 ± 1.13 µg/mL, making it a promising candidate for future studies of Alzheimer's disease.

Chemical characterization, nematicidal and antioxidant activities of Thymus linearis Benth.

Thymus linearis and its essential oil (EO) are used to cure a range of diseases in traditional medicine. GC-MS analysis of Thymus linearis EO revealed the presence of sixty-four components. Thymol (50.62%), carvacrol (13.23 %), carvacrol acetate (7.72%), -bisabolene (5.47%) and o-cymene (5.47%) are the only five basic constituents in the oil which accounts for 82.07% of oil. When compared to other compounds, the EO and its primary components thymol and carvacrol had the largest proportion of mortality in Meloidogyne javanica. Carvacrol has also been proven to be helpful in suppressing the hatching of M. javanica eggs. This is the first time T. linearis EO and its constituents, such as borneol and caryophyllene, have been studied for nematicidal action. The antioxidant activity of EO components and active compounds was assessed using the ABTS radical scavenging method. Thymol and carvacrol were found to exhibit high antioxidant activity. The IC50 of thymol and carvacrol are found to be 38.18 g/ml and 49.65 g/ml, respectively and are comparable to the positive control trolox (47.12 g/ml). Results clearly showed high potency for EO and its constituents, thymol and carvacrol as nematicidal and antioxidant agents.

Conarubins A-D: Four Monoterpene-Chalcone Conjugates from Conamomum rubidum and Their Anti-inflammatory and Cytotoxic Activities.

Four novel compounds, conarubins A-D (1-4), were isolated from the whole plants of Conamomum rubidum collected in Vietnam. Their structures were elucidated by extensive spectroscopic analyses and by quantum chemical calculations of NMR and ECD. Compounds 1 and 2 were the first examples of monoterpene-monoterpene-chalcone conjugates in nature, whereas compound 4 was an unprecedented monoterpene-substituted chalcone containing a 3,4,5-trioxygenated cyclohexa-2,5-diene-1-one ring. The anti-inflammatory and cytotoxic activities of all isolates were investigated.

Monoterpenoids from the root bark of Acanthopanax gracilistylus and their inhibitory effects on neutrophil elastase, 5-lipoxygenase, andcyclooxygenase-2 in vitro.

Twenty-four monoterpenoids, including three previously undescribed compounds (1-3), were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). Their structures were unambiguously established based on spectroscopic analysis (HR-ESIMS, IR, 1D, and 2D NMR), and the absolute configurations of 1-3 were elucidated by comparing their experimental and calculated electronic circular dichroism spectra. In addition, the structure of 8 was confirmed by single-crystal X-ray diffraction. The inhibitory activities of 1-24 against neutrophil elastase, 5-lipoxygenase, and cyclooxygenase-2 (COX-2) were studied in vitro for the first time, and the results showed that compound 24 possessed a significant inhibitory effect on COX-2 with an IC50 value of 1.53 ± 0.10 µΜ. This research first reported the presence of monoterpenoids in Acanthopanacis Cortex, including one monoterpenoid 2 with an unusual 4/5 bicyclic lactone system, and compounds 4 and 5 have never been reported in nature.

Monoterpene indole alkaloids from the roots of Alstonia rupestris and their anti-inflammatory activity.

Four new monoterpene indole alkaloids (1-4) together with twelve known alkaloids (5-16) were isolated from the roots of Alstonia rupestris. Compound 1 was the first example of C2-symmetric heteroyohimbine-type indole alkaloid homodimer obtained from natural plant resource. Their structures were elucidated on the basis of spectroscopic data. The absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra. All compounds were evaluated for their anti-inflammatory activities by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Compound 2 showed strong NO inhibition with IC50 value of 4.2 ± 1.3 µM. Moreover, compound 2 could decrease the expressions of cyclooxygenase-2 (COX-2) and transforming growth factor beta-1 (TGF-ß1).

Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg-1·d-1, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either ß-Arrestin2 or ß-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKß/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.

Biological Activity of Bursera schlechtendalii Essential oil and the Roles of Its Chemical Components in the Wound Healing Process.

Essential oils are composed of terpenes, some of which have properties related to healing. Bursera schlechtendalii essential oil (BSEO) is used to heal superficial wounds. However, there have been no studies verifying this property. The objectives of this study were to evaluate the healing activity of BSEO in a murine model and to propose the roles of its chemical components in this process. Healing activity was evaluated by an incision model, histological analysis was performed, and tensile strength and antibacterial activity were measured. The chemical composition of BSEO was determined by gas chromatography coupled with mass spectrometry (GC-MS), and the mechanisms of action of each chemical component during the phases of the healing process were proposed. In addition, acute dermal toxicity was evaluated. BSEO showed better wound closure at the macroscopic, histological, and tensile strength levels compared to controls and had an antibacterial effect. The major compound in BSEO was α-phellandrene. However, most of the monoterpenes identified in BSEO were in agreement with information found in the literature, so the possibility of synergy between the chemical components and their different targets in the healing process was schematically proposed. BSEO was shown to be safe in the dermal toxicity evaluation.

Volatile Composition and Classification of Paeonia lactiflora Flower Aroma Types and Identification of the Fragrance-Related Genes.

Flower scent is one of the main ornamental characteristics of herbaceous peony, and the improvement of flower fragrance is a vital objective of herbaceous peony breeding. In this study, 87 herbaceous peony cultivars were divided into three groups (no/light fragrance, medium fragrance, and strong fragrance) based on their sensory evaluation scores, and 16 strong fragrance cultivars and one no fragrance cultivar were selected for subsequent analysis. Sixty-eight volatile components were detected in these 17 cultivars based on solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS), and 26 types were identified as important scent components. They were composed of terpenoids, benzenoids/phenylpropanoids, and fatty acid derivatives. According to the content and odor threshold of these main aroma components, the characteristic aroma substances of herbaceous peony were identified, including linalool, geraniol, citronellol, and phenylethyl alcohol (2-PE). The cultivars of strong scented herbaceous peony were divided into three types: rose scent, lily scent, and mixed scent. We explored the possible key genes of characteristic aroma substances in herbaceous peony petals with different odors through the qRT-PCR. The key genes encoding monoterpene biosynthesis were found to be PlDXS2, PlDXR1, PlMDS1, PlHDR1, PlGPPS3, and PlGPPS4. In addition, the linalool synthase (LIS) gene and the geraniol synthase (GES) gene were also found. PlAADC1, PlPAR1, and PlMAO1, related to the biosynthesis of 2-PE were detected, and the synthetic pathway of 2-PE was speculated. In conclusion, these findings revealed that the difference in gene expression of monoterpene and 2-PE synthesis pathway was related to the difference in the fragrance of herbaceous peony. This study explored the releasing pathway of herbaceous peony characteristic aroma substances and provided key genetic resources for fragrance improvement.

Efficient myrcene production using linalool dehydratase isomerase and rational biochemical process in Escherichia coli.

Microbial synthesis of plant-based myrcene is of great interest because of its high demand, however, achieving high biosynthetic titers remains a great challenge. Previous strategies adopted for microbial myrcene production have relied on the recruitment of a multi-step biosynthetic pathway which requires complex metabolic regulation or high activity of myrcene synthase, hindering its application. Here, we present an effective one-step biotransformation system for myrcene biosynthesis from geraniol, using a linalool dehydratase isomerase (LDI) to overcome these limitations. The truncated LDI possesses nominal activity that catalyzes the isomerization of geraniol to linalool and the subsequent dehydration to myrcene in anaerobic environment. In order to improve the robustness of engineered strains for the efficient conversion of geraniol to myrcene, rational enzyme modification and a series of biochemical process engineering were employed to maintain and improve the anaerobic catalytic activity of LDI. Finally, by introducing the optimized myrcene biosynthetic capability in the existing geraniol-production strain, we achieve de novo biosynthesis of myrcene at 1.25 g/L from glycerol during 84 h aerobic-anaerobic two-stage fermentation, which is much higher than previously reported myrcene levels. This work highlights the value of dehydratase isomerase-based biocatalytic in establishing novel biosynthetic pathways and lays a reliable foundation for the microbial synthesis of myrcene.

Predictions of the Biological Effects of Several Acyclic Monoterpenes as Chemical Constituents of Essential Oils Extracted from Plants.

Acyclic terpenes are biologically active natural products having applicability in medicine, pharmacy, cosmetics and other practices. Consequently, humans are exposed to these chemicals, and it is necessary to assess their pharmacokinetics profiles and possible toxicity. The present study considers a computational approach to predict both the biological and toxicological effects of nine acyclic monoterpenes: beta-myrcene, beta-ocimene, citronellal, citrolellol, citronellyl acetate, geranial, geraniol, linalool and linalyl acetate. The outcomes of the study emphasize that the investigated compounds are usually safe for humans, they do not lead to hepatotoxicity, cardiotoxicity, mutagenicity, carcinogenicity and endocrine disruption, and usually do not have an inhibitory potential against the cytochromes involved in the metabolism of xenobiotics, excepting CYP2B6. The inhibition of CYP2B6 should be further analyzed as this enzyme is involved in both the metabolism of several common drugs and in the activation of some procarcinogens. Skin and eye irritation, toxicity through respiration and skin-sensitization potential are the possible harmful effects revealed by the investigated compounds. These outcomes underline the necessity of in vivo studies regarding the pharmacokinetics and toxicological properties of acyclic monoterpenes so as to better establish the clinical relevance of their use.