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Journal of Applied Microbiology Jun 2021Increasing demands for bioactive compounds have motivated researchers to employ micro-organisms to produce complex natural products. Currently, Bacillus subtilis has... (Review)
Review
Increasing demands for bioactive compounds have motivated researchers to employ micro-organisms to produce complex natural products. Currently, Bacillus subtilis has been attracting lots of attention to be developed into terpenoids cell factories due to its generally recognized safe status and high isoprene precursor biosynthesis capacity by endogenous methylerythritol phosphate (MEP) pathway. In this review, we describe the up-to-date knowledge of each enzyme in MEP pathway and the subsequent steps of isomerization and condensation of C5 isoprene precursors. In addition, several representative terpene synthases expressed in B. subtilis and the engineering steps to improve corresponding terpenoids production are systematically discussed. Furthermore, the current available genetic tools are mentioned as along with promising strategies to improve terpenoids in B. subtilis, hoping to inspire future directions in metabolic engineering of B. subtilis for further terpenoid cell factory development.
Topics: Alkyl and Aryl Transferases; Bacillus subtilis; Biosynthetic Pathways; Butadienes; Erythritol; Hemiterpenes; Industrial Microbiology; Metabolic Engineering; Sugar Phosphates; Terpenes
PubMed: 33098223
DOI: 10.1111/jam.14904 -
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 -
Genes Dec 2021Terpenoids constitute the largest class of natural compounds and are extremely valuable from an economic point of view due to their extended physicochemical properties... (Review)
Review
Terpenoids constitute the largest class of natural compounds and are extremely valuable from an economic point of view due to their extended physicochemical properties and biological activities. Due to recent environmental concerns, terpene extraction from natural sources is no longer considered as a viable option, and neither is the chemical synthesis to access such chemicals due to their sophisticated structural characteristics. An alternative to produce terpenoids is the use of biotechnological tools involving, for example, the construction of enzymatic cascades (cell-free synthesis) or a microbial bio-production thanks to metabolic engineering techniques. Despite outstanding successes, these approaches have been hampered by the length of the two natural biosynthetic routes (the mevalonate and the methyl erythritol phosphate pathways), leading to dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP), the two common universal precursors of all terpenoids. Recently, we, and others, developed what we called the terpene mini-path, a robust two enzyme access to DMAPP and IPP starting from their corresponding two alcohols, dimethylallyl alcohol and isopentenol. The aim here is to present the potential of this artificial bio-access to terpenoids, either in vitro or in vivo, through a review of the publications appearing since 2016 on this very new and fascinating field of investigation.
Topics: Erythritol; Hemiterpenes; Mevalonic Acid; Organophosphorus Compounds; Terpenes
PubMed: 34946923
DOI: 10.3390/genes12121974 -
Molecules (Basel, Switzerland) Jun 2022Several non-canonical, methylated terpenes have been described as products of genetically modified recently, and the aroma properties of 28 odor-active methylated...
Several non-canonical, methylated terpenes have been described as products of genetically modified recently, and the aroma properties of 28 odor-active methylated derivatives of prenol, isoprenol, bornane, camphene, carene, citronellol, fenchol, geraniol, limonene, linalool, terpineol, and farnesol were characterized for the first time in the current study. Twelve methylated monoterpenes exhibited a particularly intense and pleasant odor and were therefore chosen for the determination of their respective odor thresholds (OTs) in comparison to their non-methylated equivalents. In addition to the determination of OTs based on the literature value for the internal standard, (2)-decenal, the threshold values of the compounds with individually determined OTs of the participants were calculated. This enabled a more precise identification of the OTs. Among the non-canonical terpenes, the lowest OTs in the air were found for 2-methyllinalool (flowery, 1.8 ng L), 2-methyl--fenchol (moldy, 3.6 ng L), 2-methylgeraniol (flowery, 5.4 ng L), 2-methylcitronellol (citrus-like, 7.2 ng L), and 4-methylgeraniol (citrus-like, 16 ng L). The derivatives of geraniol, linalool, and citronellol showed very pleasant odor impressions, which could make them interesting for use as flavoring agents in the flavor and fragrance industry.
Topics: Humans; Limonene; Monoterpenes; Odorants; Perfume; Terpenes
PubMed: 35744956
DOI: 10.3390/molecules27123827 -
Biomolecules Aug 2019Solanesol, an aliphatic terpene alcohol composed of nine isoprene units, is mainly found in solanaceous plants. Particularly, tobacco (), belonging to the Solanaceae... (Review)
Review
Solanesol, an aliphatic terpene alcohol composed of nine isoprene units, is mainly found in solanaceous plants. Particularly, tobacco (), belonging to the Solanaceae family, is the richest plant source of solanesol, and its leaves have been regarded as the ideal material for solanesol extraction. Since the discovery of solanesol in tobacco, significant progress has been achieved in research on solanesol's bioactivities, medicinal value, accumulation, extraction technology, and determination methods. Solanesol possesses strong free radical absorption ability and antioxidant activity owing to the presence of several non-conjugated double bonds. Notably, solanesol's anti-inflammatory, neuroprotective, and antimicrobial activities have been previously demonstrated. Solanesol is a key intermediate in the synthesis of coenzyme Q10, vitamin K2, and the anticancer agent synergiser -solanesyl-,'-bis(3,4-dimethoxybenzyl) ethylenediamine. Other applications of solanesol include solanesol derivative micelles for hydrophobic drug delivery, solanesol-derived scaffolds for bioactive peptide multimerization, and solanesol-anchored DNA for mediating vesicle fusion. Solanesol accumulation in plants is influenced by genetic and environmental factors, including biotic stresses caused by pathogen infections, temperature, illumination, and agronomic measures. Seven extraction technologies and seven determination methods of solanesol are also systematically summarized in the present review. This review can serve as a reference for solanesol's comprehensive application.
Topics: Animals; Chemical Fractionation; Chemistry Techniques, Analytical; Humans; Terpenes
PubMed: 31382471
DOI: 10.3390/biom9080334 -
Environmental Science & Technology Dec 2023The use of household bleach cleaning products results in emissions of highly oxidative gaseous species, such as hypochlorous acid (HOCl) and chlorine (Cl). These species...
Gas-Phase and Surface-Initiated Reactions of Household Bleach and Terpene-Containing Cleaning Products Yield Chlorination and Oxidation Products Adsorbed onto Indoor Relevant Surfaces.
The use of household bleach cleaning products results in emissions of highly oxidative gaseous species, such as hypochlorous acid (HOCl) and chlorine (Cl). These species readily react with volatile organic compounds (VOCs), such as limonene, one of the most abundant compounds found in indoor enviroments. In this study, reactions of HOCl/Cl with limonene in the gas phase and on indoor relevant surfaces were investigated. Using an environmental Teflon chamber, we show that silica (SiO), a proxy for window glass, and rutile (TiO), a component of paint and self-cleaning surfaces, act as a reservoir for adsorption of gas-phase products formed between HOCl/Cl and limonene. Furthermore, high-resolution mass spectrometry (HRMS) shows that the gas-phase reaction products of HOCl/Cl and limonene readily adsorb on both SiO and TiO. Surface-mediated reactions can also occur, leading to the formation of new chlorine- and oxygen-containing products. Transmission Fourier-transform infrared (FTIR) spectroscopy of adsorption and desorption of bleach and terpene oxidation products indicates that these chlorine- and oxygen-containing products strongly adsorb on both SiO and TiO surfaces for days, providing potential sources of human exposure and sinks for additional heterogeneous reactions.
Topics: Humans; Hypochlorous Acid; Limonene; Chlorine; Halogenation; Silicon Dioxide; Terpenes; Gases; Oxygen; Air Pollution, Indoor
PubMed: 38010858
DOI: 10.1021/acs.est.3c06656 -
Molecules (Basel, Switzerland) Nov 2023In recent years, cannabis has been proposed and promoted not only as a medicine for the treatment of a variety of illnesses, but also as an industrial crop for different...
In recent years, cannabis has been proposed and promoted not only as a medicine for the treatment of a variety of illnesses, but also as an industrial crop for different purposes. Being an agricultural product, cannabis inflorescences may be contaminated by environmental pathogens at high concentrations, which might cause health problems if not controlled. Therefore, limits have to be placed on the levels of aerobic bacteria as well as yeast and mold. To ensure the safety of cannabis plant material and related products, a remediation process has to be put in place. Gamma irradiation is a sterilization process mainly used for pharmaceuticals, foods, cosmetics, agricultural, and herbal products including cannabis plant material. This study was designed to determine the effect of irradiation on the microbial count as well as on the chemical and physical profiles of the cannabis biomass, particularly cannabinoids, terpenes, and moisture content. The full cannabinoid profile was measured by GC/FID and HPLC analysis, while terpene profile and moisture content were determined using GC/MS and Loss on Drying (LoD) methods, respectively. Analyses were conducted on the samples before and after gamma irradiation. The results showed that the minimum and maximum doses were 15 and 20.8 KiloGray (KGY), respectively. Total Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC) were determined. The study showed that irradiation has no effect on the cannabinoids and little effect on terpenes and moisture content, but it did result in the virtual sterilization of the plant material, as evidenced by the low levels of bacterial and fungal colony-forming units (CFUs) < 10 after gamma irradiation.
Topics: Cannabinoids; Cannabis; Terpenes; Saccharomyces cerevisiae; Biomass; Hallucinogens; Cannabinoid Receptor Agonists
PubMed: 38067441
DOI: 10.3390/molecules28237710 -
Nature Communications May 2022Metabolites are often unable to permeate cell membranes and are thus accumulated inside cells. We investigate whether engineered microbes can exclusively secrete...
Metabolites are often unable to permeate cell membranes and are thus accumulated inside cells. We investigate whether engineered microbes can exclusively secrete intracellular metabolites because sustainable metabolite secretion holds a great potential for mass-production of high-value chemicals in an efficient and continuous manner. In this study, we demonstrate a synthetic pathway for a metabolite trafficking system that enables lipophilic terpene secretion by yeast cells. When metabolite-binding proteins are tagged with signal peptides, metabolite trafficking is highly achievable; loaded metabolites can be precisely delivered to a desired location within or outside the cell. As a proof of concept, we systematically couple a terpene-binding protein with an export signal peptide and subsequently demonstrate efficient, yet selective terpene secretion by yeast (~225 mg/L for squalene and ~1.6 mg/L for β-carotene). Other carrier proteins can also be readily fused with desired signal peptides, thereby tailoring different metabolite trafficking pathways in different microbes. To the best of our knowledge, this is the most efficient cognate pathway for metabolite secretion by microorganisms.
Topics: Protein Sorting Signals; Saccharomyces cerevisiae; Squalene; Terpenes; beta Carotene
PubMed: 35546160
DOI: 10.1038/s41467-022-30312-9 -
Molecules (Basel, Switzerland) Jun 2020Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many...
Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose-response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% ) and evaluated their anthelmintic activity on hookworms (, a rodent parasite (), and whipworm (. We identified YP-terpenes that were effective against all three parasites. Further, YP-terpenes overcame albendazole-resistant . These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.
Topics: Albendazole; Ancylostoma; Ancylostomatoidea; Animals; Anthelmintics; Benzimidazoles; Humans; Nematoda; Nematode Infections; Saccharomyces cerevisiae; Terpenes
PubMed: 32605043
DOI: 10.3390/molecules25132958 -
Pharmacological Research Mar 2022Visceral leishmaniasis (VL) is a severe and potentially fatal neglected tropical disease, being considered a public health concern in many countries worldwide. There are... (Review)
Review
Visceral leishmaniasis (VL) is a severe and potentially fatal neglected tropical disease, being considered a public health concern in many countries worldwide. There are still no vaccines against human VL, and the existing chemotherapy is often toxic. Thereby, alternative treatments have been investigated, and byproducts from plant metabolism have been a source of promising pharmacological compounds. Terpenes are secondary metabolites that exhibit a large spectrum of therapeutic activities. Herein, we conducted a systematic review to evaluate the effects of terpenes in the treatment of VL in rodents. After an extensive search using the PubMed/MEDLINE, Scopus, and Web of Science databases, we included 34 articles in this review. Our results revealed that triterpenes were the most used terpenes by the eligible studies. Overall, terpene treatment showed no or negligible toxicity, causing an increase in the Th1-type immune response profile and nitric oxide production. It also reduced the Th2 cytokines levels and parasite load (> 90% to > 99%). Moreover, terpenes induced apoptosis by damaging the plasma membrane and inhibiting DNA topoisomerases in the parasite. The use of terpene carriers increased the terpene bioavailability in the body, preventing their rapid excretion and promoting the drug delivery at the site of Leishmania infection. Terpene derivatives showed better pharmacokinetics than the original terpenes. Altogether, the benefits of VL treatment with terpenes in preclinical studies may open new directions for other preclinical and human trials.
Topics: Drug Delivery Systems; Humans; Leishmaniasis, Visceral; Phytotherapy; Terpenes; Triterpenes
PubMed: 35124205
DOI: 10.1016/j.phrs.2022.106117