Tricyclic Sesquiterpene Research Articles

Biosynthesis of bridged tricyclic sesquiterpenes in Inula lineariifolia.

Presilphiperfolane-type sesquiterpenes represent a unique group of atypical sesquiterpenoids characterized by their distinctive tricyclic structure. They have significant potential as lead compounds for pharmaceutical and agrochemical development. Herein, we utilized a transcriptomic approach to identify a terpene synthase (TPS) gene responsible for the biosynthesis of rare presilphiperfolane-type sesquiterpenes in Inula lineariifolia, designated as IlTPS1. Through phylogenetic analysis, we have identified the evolutionary conservation of key motifs, including RR(x)8W, DDxxD, and NSE/DTE in IlTPS1, which are shared with other tricyclic sesquiterpene synthases in the TPS-a subfamily of Asteraceae plants. Subsequent biochemical characterization of recombinant IlTPS1 revealed it to be a multiproduct enzyme responsible for the synthesis of various tricyclic sesquiterpene alcohols from farnesyl diphosphate (FPP), resulting in production of seven distinct sesquiterpenes. Mass spectrometry and nuclear magnetic resonance (NMR) spectrometry identified presilphiperfolan-8β-ol and presilphiperfol-7-ene as predominant products. Furthermore, biological activity assays revealed that the products from IlTPS1 exhibited a potent antifungal activity against Nigrospora oryzae. Our study represents a significant advancement as it not only functionally identifies the first step enzyme in presilphiperfolane biosynthesis but also establishes the heterologous bioproduction of these unique sesquiterpenes.

Novel Radical Cyclization Cascade for the Unified Synthesis of the Cedrane and Clovane Sesquiterpene Skeletons

AbstractRadical cyclization cascade reactions of epoxycyclohexanes possessing alkene and alkyne side chains have been achieved. Sequential 5‐ or 6‐exo‐trig/5‐exo‐dig reactions triggered by epoxide ring opening with Cp2TiCl were found to provide a useful unified synthetic method for generating the carbon skeletons of clovane and cedrane, two tricyclic sesquiterpenes. The factors responsible for the development of stereoselectivity during cyclization are also discussed.

Exogenous methyl jasmonate (MeJA) altered phytochemical composition and enhanced the expression of PatAACT gene of in vitro culture-derived patchouli var. Sidikalang (Pogostemon cablin Benth.)

The demand for economically valuable terpenoid-derived compounds, especially those extracted from patchouli plants, is experiencing exponential growth. These compounds are potentially applied in a wide range of industrial sectors including food manufacturing, perfumeries, and pharmaceuticals. Nevertheless, there is a need for further development in patchouli plant cultivation to align with market demands. Therefore, employing robust in vitro-based propagation methods could offer significant advantages. Furthermore, this technique is also used for plant metabolites enhancement. This strategy applies the methyl jasmonate (MeJA) elicitor to boost the production of secondary metabolites. In Indonesia, patchouli var. Sidikalang is extensively cultivated in many areas. This study aims to evaluate the effect of naphtaleneacetic acid (NAA) and 6-benzylamino purine (BAP) to increase plant growth via in vitro culture. Furthermore, we also investigate the effect of MeJA on the metabolite profiles and on the AACT gene expression. Our findings revealed that the combination of 2.5 µM of BAP and 0.25 µM of NAA resulted in optimal growth and high rate of organogenesis across all growth parameters. Our data also successfully identified 50 dominant compounds, each with varying percentage areas. Notably, patchouli alcohol emerged as the primary compound in the tricyclic sesquiterpene group, consistently present in all treatment groups. Furthermore, the expression of the PatAACT gene significantly increased by 7.42-fold after treatment with MeJA at 100 µM and by 2,9-fold after treatment with MeJA at 300 µM, compared to the control. Altogether, our findings might offer new insight in P. cablin propagation and new strategy for patchouli-derived metabolites using exogenous MeJA.

COMPARATIVE ANALYSIS OF CHEMICAL COMPOSITION OF THYMUS SERPYLLUM L. AND THYMUS MARSCHALLIANUS WILLD. ESSENTIAL OILS BY GAS-LIQUID CHROMATOGRAPHY WITH MASS SPECTROMETRY DETECTION

Introduction. Plant essential oils are natural sources of the different compounds, the action of which in the macroorganism is determined by their chemical composition, depending on environmental factors, including plant species. Aim. The aim of the study was to compare the chemical composition of essential oils, obtained from the aerial parts of Thymus serpyllum L. and Thymus marschallianus Willd. (Lamiaceae). Material and methods. The plant raw materials of Thymus marschallianus were collected in the flowering phase in the Saratov region in June, the plant raw materials of Thymus serpyllum were purchased in the pharmacy network. The essential oils were obtained by Ginsberg’s steam hydrodistillation method. Analysis of their chemical composition was performed by gas-liquid chromatography with mass spectrometry detection. Results. The main components of both types of the essential oils were represented by thymol and its isomers, their mass fraction in the essential oil of T. marschallianus is 38.4, in the essential oil of T. serpyllum is 44%. The comparative analysis was carried out using the non-parametric Mann-Whitney criterion. Statistically significant differences with 95% probability were established for tricyclic sesquiterpene alkenes, the total content of which in the essential oil of T. marschallianus is 4.73%, in the essential oil of T. serpyllum – 3.59%. Conclusion. According to their chemical composition the essential oils of the mentioned plant species belong to phenolic chemotype and are similar in the major compounds.

Identification and characterization of a novel sativene synthase from Fischerella thermalis

Sesquiterpene synthases (TPS) determine the structural diversity of terpenoids, which are species specific. In this study, we report a TPS from Fischerella thermalis (named as FtTPS), recombinantly expressed as a soluble protein in Escherichia coli BL21(DE3) strain. The FtTPS protein could catalyze the conversion of farnesyl pyrophosphate (FPP) to sativene, a kind of tricyclic sesquiterpene. The optimal pH and temperature of FtTPS were 7.5 and 30 °C, respectively. The KM and Vmax values of FtTPS for FPP were 1.846 μM and 0.372 μM/min, respectively. By constructing an engineered E. coli strain carrying the FtTPS and the heterologous mevalonate (MVA) pathway genes, sativene could be detected and its yield reached 24 mg/L after 96 h cultivation. The highest yield of sativene was obtained when E.coli BL21 Star was used as the host with SBMSN medium. These results exhibited the biosynthesis of sativene for the first time.

Phytochemistry and Pharmacology of Indian Traditional Plant Hyssop (Hyssopus officinalis L.): A Review

Abstract: Hyssopus officinalis is a traditional medicinal plant that belongs to the family Lamiaceae, which has been used from centuries for various purposes like carminative, expectorant, cough reliever. It has been used for the treatment of numerous diseases in patients such as ulcers, asthma, jaundice, leprosy, dropsy, bronchitis, COPD, diabetes, AIDS, bacterial and fungal infections as an herbal remedy due to its fewer side effects and is more efficacies than other traditional medicine. Major classes of chemical compounds found in H. officinalis essential oil are bicyclic monoterpenes, monoterpenoids, acyclic monoterpenes, phenolic monoterpenoids, monocyclic monoterpenes, monocyclic sesquiterpenes, tricyclic sesquiterpenes, bicyclic sesquiterpenes, tricyclic sesquiterpenoids, straight chain saturated hydrocarbons. Some of the major chemical constituents present in the H. officinalis are β-pinene, α-pinene, 1, 8-cineole, apigenin, diosmin, caffeic acid, rosmarinic acid, cis-pinocamphone, trans-pinocamphone, iso-pinocamphone, pinocarvone, which are responsible for its various pharmacological activity. Various studies have been performed on the pharmacological activity of its extract, such as antioxidant, antimicrobial, anti-diabetic, anticancer, antiviral, anti-inflammatory, analgesic, anti-leishmanial, anthelmintic, anti-protozoal and anti-anxiety. Recently, it is use as an anticancer agent has been demonstrated by studying its cytotoxic and apoptotic effects on breast cancer and colon cancer cells. It is used as a potent antibacterial and antifungal agent was studied on the antibiotic-resistant bacterial and fungal strains recently, which can be further useful in developing herbal medicine against AMR. It is an excellent natural antioxidant due to the presence of polyphenolic compounds, and H. officinalis is used in various food industries as a source of natural antioxidants, which has minimum side effects as compared to artificial antioxidants. Furthermore, the pharmacological activity of these individual chemical constituents in H. officinalis extract still needs to be investigated for identifying the effectiveness of this plant in the natural treatment of various diseases. This review aims to collect various data regarding the traditional herbal plant hyssop (Hyssopus Officinalis), including its photochemistry, chemical structures of the phyto-constituents and pharmacological profile, along with all the pharmacological models. This plant has significant importance in the health industry, so further studies are required on its effective usage against various emerging health problems, including COVID-19, cancer, diabetes, AMR.

Microbial Biotransformation of Male Specific Pheromone α-Copaene with Cunninghamella elegans and Antibacterial Activity of Its Transformed Products

Pharmaceutical industries are increasingly turning to microbial transformation instead of chemical methods. This is because microbial biotransformation is a more effective way to produce pharmacologically active molecules with high specificity and efficient yield. Additionally, it is a step towards eco-friendly synthesis. α-Copaene (1), a tricyclic sesquiterpene, is a potent attractant of the male Mediterranean fruit fly Ceratitis capitata. This paper presents the utilization of the filamentous fungus Cunninghamella elegans TSY 0865 for large-scale biotransformation of 1. α-Copaene (1) has been incubated with Cunninghamella elegans for 11 days and extracted with CH2Cl2. Four new hydroxylated metabolites 10,13-dihydroxycopaene (2); 11,13-dihydroxycopaene (3); 11-hydroxycopaen-5-one (4); and 11-hydroxy-13-copaenic acid (5) were afforded. The structures of the new metabolites were elucidated by 1D (1H, 13C) and 2D NMR (COSY, HMBC, HMQC, and NOESY) techniques and MS analyses. Metabolite 5 exhibited significant antibacterial activity against Bacillus subtilis and Pseudomonas aeruginosa.

The effects of patchouli alcohol and combination with cisplatin on proliferation, apoptosis and migration in B16F10 melanoma cells.

Melanoma is a highly metastatic cancer with a low incidence rate, but a high mortality rate. Patchouli alcohol (PA), a tricyclic sesquiterpene, is considered the main active component in Pogostemon cablin Benth, which improves wound healing and has anti-tumorigenic activity. However, the pharmacological action of PA on anti-melanoma remains unclear. Thus, the present study aimed to investigate the role of PA in the proliferation, cell cycle, apoptosis and migration of melanoma cells. These results indicated that PA selectively inhibited the proliferation of B16F10 cells in a dose- and time-dependent manner. It induced cell cycle arrest at the G0 /G1 phase and typical morphological changes in apoptosis, such as chromatin condensation, DNA fragmentation and apoptotic bodies. In addition, PA reduced the migratory ability of B16F10 cells by upregulating E-cadherin and downregulating p-Smad2/3, vimentin, MMP-2 and MMP-9 expression. PA was also found to strongly suppress tumour growth in vivo. Furthermore, PA combined with cisplatin synergistically inhibited colony formation and migration of B16F10 cells and attenuated the development of resistance to treatment. Therefore, the results of this study indicate that PA may play a pivotal role in inducing apoptosis and reducing the migration of melanoma cells, and may thus be a potential candidate for melanoma treatment.

Structural Insights into Three Sesquiterpene Synthases for the Biosynthesis of Tricyclic Sesquiterpenes and Chemical Space Expansion by Structure-Based Mutagenesis

The cyclization of farnesyl diphosphate (FPP) into highly strained polycyclic sesquiterpenes is challenging. We here determined the crystal structures of three sesquiterpene synthases (STSs, namely, BcBOT2, DbPROS, and CLM1) catalyzing the biosynthesis of the tricyclic sesquiterpenes presilphiperfolan-8β-ol (1), Δ6-protoilludene (2), and longiborneol (3). All three STS structures contain a substrate mimic, the benzyltriethylammonium cation (BTAC), in their active sites, providing ideal templates for quantum mechanics/molecular mechanics (QM/MM) analyses toward their catalytic mechanisms. The QM/MM-based molecular dynamics (MD) simulations revealed the cascade reactions toward the enzyme products, and different key active site residues that play important roles in stabilizing reactive carbocation intermediates along the three pathways. Site-directed mutagenesis experiments confirmed the roles of these key residues and concomitantly resulted in 17 shunt products (4-20). Isotopic labeling experiments addressed the key hydride and methyl migrations toward the main and several shunt products. These combined methods provided deep insights into the catalytic mechanisms of the three STSs and demonstrated how the chemical space of STSs can rationally be expanded, which may facilitate applications in synthetic biology approaches toward pharmaceutical and perfumery agents.

Preventive Activity of Patchouli Alcohol Against Colorectal Cancer and Diabetes

Patchouli alcohol (PA) is a tricyclic sesquiterpene and the dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). It has been reported to possess diverse health-beneficial activities, including anti-inflammatory, antiobese, and anticancer activities. However, preclinical studies are required to explore the possibility of developing PA as a promising functional and promising drug for the prevention and treatment of human diseases. In this study, we used animal models to examine whether PA shows benefits in inflammation-induced colorectal cancer and obesity-induced diabetes. ApcMin/+ mice for colorectal cancer model were treated PA 0, 25 and 50 mg/kg body weight three times a week for 6 weeks along with 2% dextran sulfate sodium (DSS) in drinking water for 1 week. High-fat diet (HFD)-induced obesity mice were treated with PA 0, 25, and 50 mg/kg bodyweight three times a week for 8 weeks. Oral administration of PA to ApcMin/+ mice treated with DSS significantly suppressed formation and development of tumors in both small and large intestines. In cell culture using Caco-2 human colorectal cancer cells, treatment of culture media with PA suppressed proliferation and induced G1-phase growth arrest. In a mouse model of HFD-induced obesity, glucose tolerance tests indicated the same orally administered dose of PA to significantly reduce blood glucose. In vitro assays in differentiated C2C12 myocytes further demonstrated PA to significantly enhance glucose uptake and increase phosphorylation of 5' adenosine monophosphate-activated protein kinase and protein kinase B. This study demonstrates that PA might possess health beneficial effects on colorectal cancer and obesity-induced diabetes.

Rational reprogramming of the sesquiterpene synthase BcBOT2 yields new terpenes with presilphiperfolane skeleton

Computer-aided rational design allowed to create variants of the sesquiterpene cyclase BcBOT2 that yielded novel tricyclic presilphiperfolane-type sesquiterpenes.

Sesquiterpenoids Isolated from the Rhizomes of Genus Atractylodes.

Atractylodes plants have been used in traditional herbal medicine to treat gastrointestinal diseases and contain various chemical compounds. Sesquiterpenoids are the most important therapeutic compounds in Atractylodes rhizomes. Based on studies reported from 2000 to 2022, we classified sesquiterpenoids by their chemical skeletons and original resources. Moreover, we discussed their biosynthesis and physicochemical and pharmacological features. We reported sesquiterpenoids with skeletal moieties, such as monocyclic sesquiterpenes (bisabolene- and elemene-type), bicyclic sesquiterpenes (eudesmane-, isopterocarpolone-, hydroxycarissone-, eremophilane-, bisesquiterpenoid-, guaiane- and spirovetivane-type and eudesmane lactones) and tricyclic sesquiterpenes (cyperene- and patchoulene-type), with their biosynthetic pathways, chemical modifications and in vivo metabolites. The pharmacological activities of sesquiterpenoids as anti-inflammatory, anti-tumor, anti-diabetic and anti-microbial and for treating gastrointestinal disorders have been reported for this genus.

Metabolic engineering of Escherichia coli for the biosynthesis of α-copaene from glucose

α-Copaene, a tricyclic sesquiterpene, has broad application prospects in many fields, including food, medicine, and agriculture. The conventional plant extraction method of α-copaene is unsustainable. In this study, for the first time, the de novo biosynthesis of α-copaene from glucose was achieved using a metabolically engineered Escherichia coli strain. α-Copaene was successfully produced in the engineered strain that heterologously expressed Piper nigrum α-copaene synthase. A series of strategies were employed to enhance α-copaene biosynthesis by E. coli, including heterologous overexpression of Saccharomyces cerevisiae farnesyl diphosphate synthase, MVA pathway, and truncated 3-hydroxy-3-methylglutaryl coenzyme A reductase 1. Strain optimization led to a 78.1-fold increase in α-copaene level in E. coli. This study reports a sustainable method for α-copaene production and provides a metabolic engineering strategy for the biosynthesis of other sesquiterpenes in E. coli.

Secondary metabolites of six Siberian and Crimean Armillaria species and their in vitro phytotoxicity to pine, larch and poplar

Basidiomycetes Armillaria infect deciduous, coniferous and fruit trees, causing enormous economic damage. The role of secondary metabolites (tricyclic sesquiterpene aryl esters - melleolides) in the life cycle and pathogenesis of Armillaria is under active investigation. To date, not all species of Armillaria have been tested for the biosynthesis of melleolides. We investigated the secondary metabolite profiles of six root-pathogenic species of the genus Armillaria (A. borealis Marxmüller & Korhonen, A. cepistipes Velenovský, A. gallica Marxm, A. mellea (Vahl) P. Kummer, A. sinapina Bérubé & Dessur, A. ostoyae (Romagn.) Herink) distributed in Siberia (South Krasnoyarsk Krai, Republic of Tyva, Republic of Khakassia, Taimyr Peninsula), Russian Far East (Sikhote-Alin) and Crimea (Krymsky National Park, Chatyr-Dag Mountain Lower Plateau). A total of 15 compounds were identified in the metabolome profile. Two compounds (melleolide D and melledonal C) are synthesized by all investigated strains irrespective of their geographic location and host plant. The maximum spectrum of melleolides (7-8 compounds) was found in isolates of A. borealis, A. gallica, A. sinapina, A. ostoyae. In submerged culture, the maximum accumulation of melleolides varied from 2 up to 239 mg l-1. A mixture of melleolide D and melledonal C (1:1) synthesized by the most productive strain A. mellea Cr2-17 was first found to have a phytotoxic action on the growth parameters of the callus culture Populus balsamifera and 10-day-old conifer seedlings. A 0.5% concentration of melleolides caused a credible decrease of P. balsamifera callus raw biomass; a decrease of the viability of Larix sibirica and, which is especially significant, Pinus sylvestris seedlings; inhibition of stem and root growth processes; dechromation of foliage; loss of turgor. The occurrence of a broad range of melleolides in the metabolome profile and two common compounds in all investigated strains, with a phytotoxic action at their sufficiently high concentration, enables considering the synthesis of melleolides by Armillaria fungi as one of the possible mechanisms of their pathogenicity efficiently realized in strains characterized by overproduction of melleolides under natural conditions.

FORMULASI, KARAKTERISASI DAN UJI STABILITAS MIKROEMULSI MINYAK NILAM (Pogostemon cablin Benth.)

Patchouli oil contains patchouli alcohol as the main component which is a tricyclic tertiary alcohol sesquiterpene compound that is insoluble in water. Microemulsion is a droplet dispersion technology that combines an insoluble liquid with another liquid. The role of surfactants in helping the dispersion process of microemulsion formulation is by reducing the interfacial tension. Microemulsion is a supersolvents carrier, so that both hydrophilic and lipophilic can be administered through a microemulsion system. The purpose of this study was to formulate patchouli oil into a stable microemulsion preparation. This research was conducted by making 4 preparations of patchouli oil microemulsion containing 5% (F1), 10% (F2), and 15% (F3) patchouli oil, and microemulsion without patchouli oil (F0). Evaluation of microemulsion preparations includes organoleptic test, pH measurement, density determination, viscosity test, freeze and thaw test, centrifugation test, and particle size analysis. The test results showed that the microemulsion containing 5% patchouli oil had the most stable characteristics compared to other formulas.

Clinical Strains of Helicobacter pylori With Strong Cell Invasiveness and the Protective Effect of Patchouli Alcohol by Improving miR-30b/C Mediated Xenophagy.

Helicobacter pylori was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of H. pylori activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular H. pylori and promotes its drug resistance. This study revealed that some clinical drug-resistant H. pylori strains present much stronger invasive ability than standard strains. Patchouli alcohol (PA), a tricyclic sesquiterpene from Pogostemon cablin (Blanco) Benth (Labiatae), showed reliable activity against intracellular H. pylori. The mechanisms appeared to involve the downregulation of miR-30c-3p/5p and miR-30b-5p, thereby upregulating xenophagy-related gene expression (ULK1, ATG5, ATG12, and ATG14) and enhancing xenophagy. PA also inhibited the nuclear transfection of miR-30b-5p induced by H. pylori, thereby enhancing transcription factor EB function and increasing lysosome activity. The finding of strongly invasive intracellular H. pylori has great implications for clinical treatment, and PA can act against invasive H. pylori based on the improvement of miR-30b/c mediated xenophagy. Taken together, the results demonstrate that PA have potential use as a candidate medication for intracellular drug-resistant H. pylori.

High-Level Production of Sesquiterpene Patchoulol in Saccharomyces cerevisiae.

Patchoulol is a tricyclic sesquiterpene widely used in perfumes and cosmetics. Herein, comprehensive engineering strategies were employed to construct an efficient yeast strain for patchoulol production. First, a platform strain was constructed via pathway modification. Second, three off-pathway genes were deleted, which led to significant physiological changes in yeast. Further, strengthening of the ergosterol pathway, enhancement of the energy supply, and a decrease in intracellular reactive oxygen species were implemented to improve the physiological status of yeast, demonstrating a new promotive relationship between ergosterol biosynthesis and synthesis of patchoulol. Moreover, patchoulol synthase was improved through protein modification and Mg2+ addition, reaching a final titer of 141.5 mg/L in a shake flask. Finally, a two-stage fermentation with dodecane addition was employed to achieve the highest production (1632.0 mg/L, 87.0 mg/g dry cell weight, 233.1 mg/L/d) ever reported for patchoulol in a 5 L bioreactor. This work lays a foundation for green and efficient patchoulol production.

Isolongifolene mitigates rotenone-induced dopamine depletion and motor deficits through anti-oxidative and anti-apoptotic effects in a rat model of Parkinson's disease

Isolongifolene (ILF), a novel tricyclic sesquiterpene compound isolated from the Indian herb Murraya koenigii (M. koenigii), has been previously demonstrated to have a neuroprotective effect against rotenone-induced oxidative stress, mitochondrial dysfunction, and apoptosis in in vitro model. However, these neuroprotective and anti-apoptotic effects of ILF are not well understood and must be further investigated to elucidate the underlying molecular mechanism of ILF in animal experiments. The objective of this study was to evaluate the neuroprotective effect of ILF on motor impediments, neurochemical variables, anti-oxidative indices, and apoptotic protein expression in a rotenone-induced rat model of Parkinson's disease (PD). PD was induced in male albino Wistar rats via injection of 2.5 mg/kg rotenone for 4 weeks. Rotenone produces PD-like effects by promoting mitochondrial complex I inhibition and microglial activation properties. The protective effect of three different doses of ILF 5, 10 and 20 mg/kg were evaluated for spontaneous locomotion, rotarod performance, and striatal dopamine (DA) content. The results showed that ILF dose-dependently ameliorated the rotenone-induced striatal DA loss and motor impairment from 10 mg/kg. Therefore, we selected 10 mg/kg as the ILF dose for further investigation. Chronic administration of rotenone caused PD-related pathological processes like oxidative stress, and produced a significant decrease in tyrosine hydroxylase (TH), DA transporter (DAT), Vesicular monoamine transporter 2 (VMAT2), and a significant upregulated in α-synuclein and apoptotic protein expression of Bax, Cyt-C and caspases -3, -8 and −9 as well as by decreasing Bcl2 expression. Treatment with ILF 10 mg/kg mitigated oxidative stress in rotenone-treated rats. Furthermore, ILF dramatically alleviated rotenone-induced toxicity and cell death by increasing TH, DAT and VMAT2 expression and reducing the upregulation of α-synuclein, Bax, Cyt-C, caspases -3, -8 and -9. Together, our results confirm that ILF’s protective effect against rotenone-induced PD is mediated through anti-oxidant and anti-apoptotic properties. However, further in-depth investigations on ILF’s anti-inflammatory and mitochondrial protective abilities are needed to establish ILF as a potential drug candidate for the treatment of Parkinson’s disease.

Conversion of poplar biomass into high-energy density tricyclic sesquiterpene jet fuel blendstocks

BackgroundIn an effort to ensure future energy security, reduce greenhouse gas emissions and create domestic jobs, the US has invested in technologies to develop sustainable biofuels and bioproducts from renewable carbon sources such as lignocellulosic biomass. Bio-derived jet fuel is of particular interest as aviation is less amenable to electrification compared to other modes of transportation and synthetic biology provides the ability to tailor fuel properties to enhance performance. Specific energy and energy density are important properties in determining the attractiveness of potential bio-derived jet fuels. For example, increased energy content can give the industry options such as longer range, higher load or reduced takeoff weight. Energy-dense sesquiterpenes have been identified as potential next-generation jet fuels that can be renewably produced from lignocellulosic biomass.ResultsWe developed a biomass deconstruction and conversion process that enabled the production of two tricyclic sesquiterpenes, epi-isozizaene and prespatane, from the woody biomass poplar using the versatile basidiomycete Rhodosporidium toruloides. We demonstrated terpene production at both bench and bioreactor scales, with prespatane titers reaching 1173.6 mg/L when grown in poplar hydrolysate in a 2 L bioreactor. Additionally, we examined the theoretical fuel properties of prespatane and epi-isozizaene in their hydrogenated states as blending options for jet fuel, and compared them to aviation fuel, Jet A.ConclusionOur findings indicate that prespatane and epi-isozizaene in their hydrogenated states would be attractive blending options in Jet A or other lower density renewable jet fuels as they would improve viscosity and increase their energy density. Saturated epi-isozizaene and saturated prespatane have energy densities that are 16.6 and 18.8% higher than Jet A, respectively. These results highlight the potential of R. toruloides as a production host for the sustainable and scalable production of bio-derived jet fuel blends, and this is the first report of prespatane as an alternative jet fuel.

Penisarins A and B, Sesquiterpene Coumarins Isolated from an Endophytic Penicillium sp.

Penisarins A (1) and B (2), sesquiterpene coumarins with an unusual tricyclic sesquiterpene system, were isolated from endophytic Penicillium sp. KMU18029. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 2 showed significant cytotoxicities against two human cancer cell lines, HL-60 and SMMC-7721, with IC50 values of 3.6 ± 0.2 and 3.7 ± 0.2 μM, respectively.