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Molecules (Basel, Switzerland) Dec 2020Terpenes are the primary constituents of essential oils and are responsible for the aroma characteristics of cannabis. Together with the cannabinoids, terpenes... (Review)
Review
Terpenes are the primary constituents of essential oils and are responsible for the aroma characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or entourage effect and their interactions have only been speculated in for the last few decades. Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely to the consumer's experiences and market price. They also enhance many therapeutic benefits, especially as aromatherapy. To shed light on the importance of terpenes in the cannabis industry, the purpose of this review is to morphologically describe sources of cannabis terpenes and to explain the biosynthesis and diversity of terpene profiles in different cannabis chemovars.
Topics: Biosynthetic Pathways; Cannabinoids; Cannabis; Oils, Volatile; Phenotype; Terpenes; Volatile Organic Compounds
PubMed: 33302574
DOI: 10.3390/molecules25245792 -
Molecules (Basel, Switzerland) Nov 2019Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However,... (Review)
Review
Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However, these highly functionalized natural products are produced through complex biosynthetic pathways for which we have a complete understanding in only a few cases. Here we review some of the most effective and promising plant terpenoids that are currently used in medicine and medical research and provide updates on their biosynthesis, natural occurrence, and mechanism of action in the body. This includes pharmacologically useful plastidic terpenoids such as -menthane monoterpenoids, cannabinoids, paclitaxel (taxol), and ingenol mebutate which are derived from the 2--methyl-d-erythritol-4-phosphate (MEP) pathway, as well as cytosolic terpenoids such as thapsigargin and artemisinin produced through the mevalonate (MVA) pathway. We further provide a review of the MEP and MVA precursor pathways which supply the carbon skeletons for the downstream transformations yielding these medically significant natural products.
Topics: Animals; Biosynthetic Pathways; Cannabinoids; Diterpenes; Erythritol; Herbal Medicine; Humans; Mevalonic Acid; Monoterpenes; Paclitaxel; Sugar Phosphates; Terpenes; Thapsigargin
PubMed: 31683764
DOI: 10.3390/molecules24213961 -
Nature Communications Jan 2020The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and...
The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations.
Topics: Biosynthetic Pathways; Monoterpenes; Oxidation-Reduction; Stereoisomerism; Terpenes
PubMed: 31980637
DOI: 10.1038/s41467-020-14354-5 -
Current Neuropharmacology 2020Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with... (Review)
Review
Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, 'cannabis' is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the "entourage effect" is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.
Topics: Animals; Anxiety Disorders; Cannabinoids; Humans; Mood Disorders; Terpenes
PubMed: 31481004
DOI: 10.2174/1570159X17666190903103923 -
Natural Product Reports Mar 2020Covering: up to July 2019 Terpene synthases (TSs) are responsible for generating much of the structural diversity found in the superfamily of terpenoid natural products.... (Review)
Review
Covering: up to July 2019 Terpene synthases (TSs) are responsible for generating much of the structural diversity found in the superfamily of terpenoid natural products. These elegant enzymes mediate complex carbocation-based cyclization and rearrangement cascades with a variety of electron-rich linear and cyclic substrates. For decades, two main classes of TSs, divided by how they generate the reaction-triggering initial carbocation, have dominated the field of terpene enzymology. Recently, several novel and unconventional TSs that perform TS-like reactions but do not resemble canonical TSs in sequence or structure have been discovered. In this review, we identify 12 families of non-canonical TSs and examine their sequences, structures, functions, and proposed mechanisms. Nature provides a wide diversity of enzymes, including prenyltransferases, methyltransferases, P450s, and NAD+-dependent dehydrogenases, as well as completely new enzymes, that utilize distinctive reaction mechanisms for TS chemistry. These unique non-canonical TSs provide immense opportunities to understand how nature evolved different tools for terpene biosynthesis by structural and mechanistic characterization while affording new probes for the discovery of novel terpenoid natural products and gene clusters via genome mining. With every new discovery, the dualistic paradigm of TSs is contradicted and the field of terpene chemistry and enzymology continues to expand.
Topics: Alkyl and Aryl Transferases; Aminophenols; Cannabinoids; Cyclization; Cytochrome P-450 Enzyme System; Dimethylallyltranstransferase; Iridoids; Lyngbya Toxins; Molecular Structure; Phenazines; Polycyclic Compounds; Protein Conformation; Terpenes
PubMed: 31650156
DOI: 10.1039/c9np00051h -
Marine Drugs Nov 2021Organic extracts of marine invertebrates, mainly sponges, from seas all over the world are well known for their high in vitro anticancer and antibiotic activities which... (Review)
Review
Organic extracts of marine invertebrates, mainly sponges, from seas all over the world are well known for their high in vitro anticancer and antibiotic activities which make them promising sources of compounds with potential use as pharmaceutical leads. Most of the structures discovered so far have a peculiar structural feature in common: a 1,2-dioxane ring. This is a highly reactive heterocycle that can be considered as an endoperoxide function. Together with other structural features, this group could be responsible for the strong biological activities of the substances present in the extracts. Numerous research programs have focused on their structural elucidation and total synthesis since the seventies. As a consequence, the number of established chiral centres and the similarity between different naturally occurring substances is increasingly higher. Most of these compounds have a terpenoid nature, mainly diterpene and sesterterpene, with several peculiar structural features, such as the loss of one carbon atom. Although there are many reviews dealing with the occurrence of marine peroxides, their activities, or potential pharmaceutical uses, no one has focused on those having a terpene origin and the endoperoxide function. We present here a comprehensive review of these compounds paying special attention to their structural features and their biological activity.
Topics: Animals; Aquatic Organisms; Peroxides; Porifera; Structure-Activity Relationship; Terpenes
PubMed: 34940660
DOI: 10.3390/md19120661 -
World Journal of Microbiology &... May 2023Terpenes and terpenoids are a group of isoprene-derived molecules that constitute the largest group of natural products and secondary metabolites produced by living... (Review)
Review
Terpenes and terpenoids are a group of isoprene-derived molecules that constitute the largest group of natural products and secondary metabolites produced by living things, with more than 25,000 compounds reported. These compounds are synthesized by enzymes called terpene synthases, which include several families of cyclases and enzymes. These are responsible for adding functional groups to cyclized structures. Fungal terpenoids are of great interest for their pharmacological properties; therefore, understanding the mechanisms that regulate their synthesis (regulation of the mevalonate pathway, regulation of gene expression, and availability of cofactors) is essential to direct their production. For this reason, this review addresses the detailed study of the biosynthesis of fungal terpenoids and their regulation by various physiological and environmental factors.
Topics: Terpenes; Fungi; Alkyl and Aryl Transferases; Fungal Proteins
PubMed: 37169980
DOI: 10.1007/s11274-023-03635-y -
Plant Physiology Sep 2020Cannabis () resin is the foundation of a multibillion dollar medicinal and recreational plant bioproducts industry. Major components of the cannabis resin are the...
Cannabis () resin is the foundation of a multibillion dollar medicinal and recreational plant bioproducts industry. Major components of the cannabis resin are the cannabinoids and terpenes. Variations of cannabis terpene profiles contribute much to the different flavor and fragrance phenotypes that affect consumer preferences. A major problem in the cannabis industry is the lack of proper metabolic characterization of many of the existing cultivars, combined with sometimes incorrect cultivar labeling. We characterized foliar terpene profiles of plants grown from 32 seed sources and found large variation both within and between sets of plants labeled as the same cultivar. We selected five plants representing different cultivars with contrasting terpene profiles for clonal propagation, floral metabolite profiling, and trichome-specific transcriptome sequencing. Sequence analysis of these five cultivars and the reference genome of cv Purple Kush revealed a total of 33 different cannabis terpene synthase () genes, as well as variations of the gene family and differential expression of terpenoid and cannabinoid pathway genes between cultivars. Our annotation of the cv Purple Kush reference genome identified 19 complete gene models, and tandem arrays of isoprenoid and cannabinoid biosynthetic genes. An updated phylogeny of the gene family showed three cannabis-specific clades, including a clade of sesquiterpene synthases within the TPS-b subfamily that typically contains mostly monoterpene synthases. The CsTPSs described and functionally characterized here include 13 that had not been previously characterized and that collectively explain a diverse range of cannabis terpenes.
Topics: Alkyl and Aryl Transferases; Cannabis; Phylogeny; Plant Proteins; Terpenes
PubMed: 32591428
DOI: 10.1104/pp.20.00593 -
Plant Communications Sep 2021Terpenes, the largest group of plant-specialized metabolites, have received considerable attention for their highly diverse biological activities. Monoterpenes (C10),... (Review)
Review
Terpenes, the largest group of plant-specialized metabolites, have received considerable attention for their highly diverse biological activities. Monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and triterpenes (C30) have been extensively investigated at both the biochemical and molecular levels over the past two decades. Sesterterpenes (C25), an understudied terpenoid group, were recently described by plant scientists at the molecular level. This review summarizes the plant species that produce sesterterpenes and describes recent developments in the field of sesterterpene biosynthesis, placing a special focus on the catalytic mechanism and evolution of geranylfarnesyl diphosphate synthase and sesterterpene synthase. Finally, we propose several questions to be addressed in future studies, which may help to elucidate sesterterpene metabolism in plants.
Topics: Plants; Sesterterpenes
PubMed: 34746758
DOI: 10.1016/j.xplc.2021.100184 -
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