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PloS One 2020Terpenes are the largest class of natural products with extensive structural diversity and are widely used as pharmaceuticals, herbicides, flavourings, fragrances, and...
Terpenes are the largest class of natural products with extensive structural diversity and are widely used as pharmaceuticals, herbicides, flavourings, fragrances, and biofuels. While they have mostly been isolated from plants and fungi, the availability and analysis of bacterial genome sequence data indicates that bacteria also possess many putative terpene synthase genes. In this study, we further explore this potential for terpene synthase activity in bacteria. Twenty two potential class I terpene synthase genes (TSs) were selected to represent the full sequence diversity of bacterial synthase candidates and recombinantly expressed in E. coli. Terpene synthase activity was detected for 15 of these enzymes, and included mono-, sesqui- and diterpene synthase activities. A number of confirmed sesquiterpene synthases also exhibited promiscuous monoterpene synthase activity, suggesting that bacteria are potentially a richer source of monoterpene synthase activity then previously assumed. Several terpenoid products not previously detected in bacteria were identified, including aromandendrene, acora-3,7(14)-diene and longiborneol. Overall, we have identified promiscuous terpene synthases in bacteria and demonstrated that terpene synthases with substrate promiscuity are widely distributed in nature, forming a rich resource for engineering terpene biosynthetic pathways for biotechnology.
Topics: Alkyl and Aryl Transferases; Bacteria; Biosynthetic Pathways; Genome, Bacterial; Phylogeny; Terpenes
PubMed: 32353014
DOI: 10.1371/journal.pone.0232220 -
International Journal of Hygiene and... Apr 2020Reactive chemistry is ubiquitous indoors with a wealth of complex oxidation reactions; some of these are initiated by both homogeneous and heterogeneous reaction of... (Review)
Review
Reactive chemistry is ubiquitous indoors with a wealth of complex oxidation reactions; some of these are initiated by both homogeneous and heterogeneous reaction of ozone with unsaturated organic compounds and subsequent the hydroxyl radical, either in the gas-phase or on reactive surfaces. One major focus has been the reaction of common and abundant terpene-based fragrances in indoor air emitted from many wood-based materials, a variety of consumer products, and citrus fruits and flowers. Inhalation of the terpenes themselves are generally not considered a health concern (both acute and long-term) due to their low indoor air concentrations; however, their gas- and surface reactions with ozone and the hydroxyl radical produce a host of products, both gaseous, i. a. formaldehyde, and ultrafine particles formed by condensation/nucleation processes. These reaction products may be of health concern. Human cell bioassays with key reaction products from ozone-initiated terpene reactions have shown some inflammatory reactions, but results are difficult to interpret for human exposure and risk assessment. Acute effects like sensory irritation in eyes and airways are unlikely or present at very low intensity in real life conditions based on rodent and human exposure studies and known thresholds for sensory irritation in eyes and airways and derived human reference values for airflow limitation and pulmonary irritation. Some fragrances and their ozone-initiated reaction products may possess anti-inflammatory properties. However, long-term effects of the reaction products as ultrafine particles are poorly explored. Material and product surfaces with high ozone deposition velocities may significantly impact the perceived air quality by altered emissions from both homogeneous and heterogeneous surface reactions.
Topics: Air Pollutants; Air Pollution, Indoor; Animals; Humans; Inhalation Exposure; Lung; Risk Assessment; Terpenes
PubMed: 32044535
DOI: 10.1016/j.ijheh.2019.113439 -
Accounts of Chemical Research Apr 2020From structure elucidation and biogenesis to synthetic methodology and total synthesis, terpene natural products have profoundly influenced the development of organic... (Review)
Review
From structure elucidation and biogenesis to synthetic methodology and total synthesis, terpene natural products have profoundly influenced the development of organic chemistry. Moreover, their myriad functional attributes range from fragrance to pharmaceuticals and have had great societal impact. Ruzicka's formulation of the "biogenetic isoprene rule," a Nobel Prize winning discovery now over 80 years old, allowed for identification of higher order terpene (aka "isoprenoid") structures from simple five-carbon isoprene fragments. Notably, the isoprene rule still holds pedagogical value to students of organic chemistry today. Our laboratory has completed syntheses of over two dozen terpene and meroterpene structures to date, and the isoprene rule has served as a key pattern recognition tool for our synthetic planning purposes. At the strategic level, great opportunity exists in finding unique and synthetically simplifying ways to connect the formal C isoprene fragments embedded in terpenes. Biomimetic cationic polyene cyclizations represent the earliest incarnation of this idea, which has facilitated expedient routes to certain terpene polycycle classes. Nonetheless, a large swath of terpene chemical space remains inaccessible using this approach.In this Account, we describe strategic insight into our endeavors in terpene synthesis published over the last five years. We show how biosynthetic understanding, combined with a desire to utilize abundant and inexpensive [C] building blocks, has led to efficient, abiotic syntheses of multiple complex terpenes with disparate ring systems. Informed by nature, but unconstrained by its processes, our synthetic assembly exploits chemical reactivity across diverse reaction types-including radical, anionic, pericyclic, and metal-mediated transformations.First, we detail an eight-step synthesis of the cembrane diterpene chatancin from dihydrofarnesal using a bioinspired-but not -mimetic-cycloaddition. Next, we describe the assembly of the antimalarial cardamom peroxide using a polyoxygenation cascade to fuse multiple units of molecular oxygen onto a dimeric skeleton. This three-to-four-step synthesis arises from (-)-myrtenal, an inexpensive pinene oxidation product. We then show how a radical cyclization cascade can forge the hallmark cyclooctane ring system of the complex sesterterpene 6--ophiobolin N from two simple polyprenyl precursors, (-)-linalool and farnesol. To access the related, more complex metabolite 6-ophiobolin A, we exploited the plasticity of our synthetic route and found that use of geraniol (C) rather than farnesol (C) gave us the flexibility needed to address the additional oxidation found in this congener. Following this work, we describe two strategies to access several guaianolide sesquiterpenes. Retrosynthetic disconnection to monoterpenes, carvone or (-)-linalool, coupled with a powerful allylation strategy allowed us to address guaianolides with disparate stereochemical motifs. Finally, we examine a semisynthetic approach to the sesquiterpenes from the abundant 15-carbon feedstock terpene (+)-cedrol using an abiotic ring shift and multiple C-H oxidation reactions inspired by a postulated biosynthesis of this natural product class.
Topics: Chemistry Techniques, Synthetic; Neoprene; Terpenes
PubMed: 32202757
DOI: 10.1021/acs.accounts.0c00055 -
Scientific Reports Jun 2020Carrot (Daucus carota L.) is an important root vegetable crop with high nutritional value, characteristic flavor, and benefits to human health. D. carota tissues produce...
Carrot (Daucus carota L.) is an important root vegetable crop with high nutritional value, characteristic flavor, and benefits to human health. D. carota tissues produce an essential oil that is rich in volatile terpenes and plays a major role in carrot aroma and flavor. Although terpene composition represents a critical quality attribute of carrots, little is known about the biosynthesis of terpenes in this crop. Here, we functionally characterized 19 terpene synthase (TPS) genes in an orange carrot (genotype DH1) and compared tissue-specific expression profiles and in vitro products of their recombinant proteins with volatile terpene profiles from DH1 and four other colored carrot genotypes. In addition to the previously reported (E)-β-caryophyllene synthase (DcTPS01), we biochemically characterized several TPS proteins with direct correlations to major compounds of carrot flavor and aroma including germacrene D (DcTPS7/11), γ-terpinene (DcTPS30) and α-terpinolene (DcTPS03). Random forest analysis of volatiles from colored carrot cultivars identified nine terpenes that were clearly distinct among the cultivars and likely contribute to differences in sensory quality. Correlation of TPS gene expression and terpene metabolite profiles supported the function of DcTPS01 and DcTPS03 in these cultivars. Our findings provide a roadmap for future breeding efforts to enhance carrot flavor and aroma.
Topics: Alkyl and Aryl Transferases; Daucus carota; Gene Expression Regulation, Plant; Odorants; Oils, Volatile; Plant Proteins; Terpenes
PubMed: 32561772
DOI: 10.1038/s41598-020-66866-1 -
Angewandte Chemie (International Ed. in... Jan 2012Terpenes are the largest class of small-molecule natural products on earth, and the most abundant by mass. Here, we summarize recent developments in elucidating the... (Review)
Review
Terpenes are the largest class of small-molecule natural products on earth, and the most abundant by mass. Here, we summarize recent developments in elucidating the structure and function of the proteins involved in their biosynthesis. There are six main building blocks or modules (α, β, γ, δ, ε, and ζ) that make up the structures of these enzymes: the αα and αδ head-to-tail trans-prenyl transferases that produce trans-isoprenoid diphosphates from C(5) precursors; the ε head-to-head prenyl transferases that convert these diphosphates into the tri- and tetraterpene precursors of sterols, hopanoids, and carotenoids; the βγ di- and triterpene synthases; the ζ head-to-tail cis-prenyl transferases that produce the cis-isoprenoid diphosphates involved in bacterial cell wall biosynthesis; and finally the α, αβ, and αβγ terpene synthases that produce plant terpenes, with many of these modular enzymes having originated from ancestral α and β domain proteins. We also review progress in determining the structure and function of the two 4Fe-4S reductases involved in formation of the C(5) diphosphates in many bacteria, where again, highly modular structures are found.
Topics: Farnesyl-Diphosphate Farnesyltransferase; Humans; Metalloproteins; Terpenes
PubMed: 22105807
DOI: 10.1002/anie.201103110 -
International Journal of Molecular... Jul 2023Secondary metabolism plays an important role in the adaptation of plants to their environments, particularly by mediating bio-interactions and protecting plants from... (Review)
Review
Secondary metabolism plays an important role in the adaptation of plants to their environments, particularly by mediating bio-interactions and protecting plants from herbivores, insects, and pathogens. Terpenoids form the largest group of plant secondary metabolites, and their biosynthesis and regulation are extremely complicated. Terpenoids are key players in the interactions and defense reactions between plants, microorganisms, and animals. Terpene compounds are of great significance both to plants themselves and the ecological environment. On the one hand, while protecting plants themselves, they can also have an impact on the environment, thereby affecting the evolution of plant communities and even ecosystems. On the other hand, their economic value is gradually becoming clear in various aspects of human life; their potential is enormous, and they have broad application prospects. Therefore, research on terpenoids is crucial for plants, especially crops. This review paper is mainly focused on the following six aspects: plant terpenes (especially terpene volatiles and plant defense); their ecological functions; their biosynthesis and transport; related synthesis genes and their regulation; terpene homologues; and research and application prospects. We will provide readers with a systematic introduction to terpenoids covering the above aspects.
Topics: Animals; Humans; Terpenes; Ecosystem; Plants; Herbivory
PubMed: 37511319
DOI: 10.3390/ijms241411561 -
Chemical Research in Toxicology Apr 2023Vaping devices have risen in popularity since their inception in 2007. The practice involves using a variety of commercially available devices. Internal heating systems...
Vaping devices have risen in popularity since their inception in 2007. The practice involves using a variety of commercially available devices. Internal heating systems in devices aerosolize e-liquid formulations of complex mixtures including an active ingredient (e.g., THC, CBD, and nicotine), diluents (or cutting agents), solvents, and flavoring agents (e.g., terpenes and aldehydes). The vaping toxicology literature consists of cytotoxicity studies of individual chemicals and commercial formulas. Because of the variation of e-liquid composition, there is a limited understanding of the toxicity of ingredient combinations. This study analyzed the cytotoxic effects after exposure to individual and binary mixtures of a representative terpene (+--limonene) and diluent (triethyl citrate) on human lung cell models. Data were analyzed to determine the effects of 97:3 and 80:20% v/v (triethyl citrate/limonene) binary mixtures. BEAS-2B cells, a bronchial epithelial cell, and A549 cells, a type II alveolar epithelial cell, served as models for comparison. LC values were calculated and isobolograms were used to assess chemical interactions. Results show that limonene was more cytotoxic than triethyl citrate. Isobolographic analyses confirmed that the 97:3% v/v mixture resulted in an antagonistic chemical interaction. The 80:20% v/v mixture resulted in a similar result. Further testing of different ratios of binary mixtures is needed for chemical interaction screening to inform safety assessments.
Topics: Humans; Terpenes; Limonene; Vaping; Citrates; Electronic Nicotine Delivery Systems
PubMed: 36279315
DOI: 10.1021/acs.chemrestox.2c00218 -
International Journal of Molecular... Apr 2023Terpenes, especially volatile terpenes, are important components of tea aroma due to their unique scents. They are also widely used in the cosmetic and medical... (Review)
Review
Terpenes, especially volatile terpenes, are important components of tea aroma due to their unique scents. They are also widely used in the cosmetic and medical industries. In addition, terpene emission can be induced by herbivory, wounding, light, low temperature, and other stress conditions, leading to plant defense responses and plant-plant interactions. The transcriptional levels of important core genes (including , , and ) involved in terpenoid biosynthesis are up- or downregulated by the MYB, MYC, NAC, ERF, WRKY, and bHLH transcription factors. These regulators can bind to corresponding cis-elements in the promoter regions of the corresponding genes, and some of them interact with other transcription factors to form a complex. Recently, several key terpene synthesis genes and important transcription factors involved in terpene biosynthesis have been isolated and functionally identified from tea plants. In this work, we focus on the research progress on the transcriptional regulation of terpenes in tea plants () and thoroughly detail the biosynthesis of terpene compounds, the terpene biosynthesis-related genes, the transcription factors involved in terpene biosynthesis, and their importance. Furthermore, we review the potential strategies used in studying the specific transcriptional regulation functions of candidate transcription factors that have been discriminated to date.
Topics: Terpenes; Camellia sinensis; Gene Expression Regulation, Plant; Transcription Factors; Tea; Plant Proteins
PubMed: 37108101
DOI: 10.3390/ijms24086937 -
Channels (Austin, Tex.) Dec 2019Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through...
Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the component myrcene have been suggested as pain therapeutics, we screened terpenes found in for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced calcium flux responses. Terpenes contribute differentially to calcium fluxes via TRPV1 induced by -mimetic cannabinoid/terpenoid mixtures. Myrcene dominates the TRPV1-mediated calcium responses seen with terpenoid mixtures. Myrcene-induced calcium influx is inhibited by the TRPV1 inhibitor capsazepine and Myrcene elicits TRPV1 currents in the whole-cell patch-clamp configuration. TRPV1 currents are highly sensitive to internal calcium. When Myrcene currents are evoked, they are distinct from capsaicin responses on the basis of I and their lack of shift to a pore-dilated state. Myrcene pre-application and residency at TRPV1 appears to negatively impact subsequent responses to TRPV1 ligands such as Cannabidiol, indicating allosteric modulation and possible competition by Myrcene. Molecular docking studies suggest a non-covalent interaction site for Myrcene in TRPV1 and identifies key residues that form partially overlapping Myrcene and Cannabidiol binding sites. We identify several non- plant-derived sources of Myrcene and other compounds targeting nociceptive TRPs using a data mining approach focused on analgesics suggested by non-Western Traditional Medical Systems. These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.
Topics: Acyclic Monoterpenes; Alkenes; Calcium; Cannabinoids; Cannabis; Cell Line; Humans; Models, Molecular; Molecular Docking Simulation; Plant Extracts; TRPA1 Cation Channel; Terpenes
PubMed: 31446830
DOI: 10.1080/19336950.2019.1654347 -
Plant Science : An International... Jul 2019Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global... (Review)
Review
Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans. Cannabis resin contains hundreds of different terpene and cannabinoid metabolites. Many of these metabolites have not been conclusively identified. Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis 'strains'. Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation.
Topics: Cannabinoids; Cannabis; Genetic Variation; Genome, Plant; Genotype; Genotyping Techniques; Metabolic Networks and Pathways; Terpenes
PubMed: 31084880
DOI: 10.1016/j.plantsci.2019.03.022