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Terpenoids are natural compounds predominantly present in plants. They have many pharmaceutical and/or nutritional functions, and have been widely applied in medical, food, and cosmetics industries. Recently, terpenoids have been used in the clinical treatment of COVID-19 due to the good antiviral activities. The increasing demand for terpenoids in international markets poses a serious threat to many plant species. For environmentally sustainable development, microbial cell factories have been utilized as the promising platform to produce terpenoids. Nevertheless, the bioproduction of most terpenoids cannot meet commercial requirements due to the low cost-benefit ratio until now. The biosynthetic potential of endophytes has gained attention in recent decades owing to the continual discovery of endophytes capable of synthesizing plant bioactive compounds. Accordingly, endophytes could be alternative sources of terpenoid-producing strains or terpenoid synthetic genes. In this review, we summarized the research progress describing the main and supporting roles of endophytes in terpenoid biosynthesis and biotransformation, and discussed the current problems and challenges which may prevent the further exploitation. This review will improve our understanding of endophyte resources for terpenoid production in industry in the future. Key points • The mechanisms employed by endophytes in terpenoid synthesis in vivo and in vitro. • Endophytes have the commercial potentials in terpenoid bioproduction and biotransformation. • Synthetic biology and multiomics will improve terpenoid bioproduction in engineered cell factories. [ABSTRACT FROM AUTHOR]

Aster tataricus L.f. is highly valued for its rich reserves of bioactive compounds. Our research focused on the identification of previously unreported compounds found within the ethanol extract of A. tataricus. Through meticulous spectroscopic analyses and computational methods like NMR calculations and ECD, we successfully elucidated the structures of five novel compounds termed tatarisides A-E (1–5), alongside two known compounds (6, 7). The anti-inflammatory assays conducted yielded noteworthy results, particularly in relation to compounds 1 and 5. These compounds exhibited significant potential in inhibiting the release of NO in LPS-induced RAW 264.7 cells, as evidenced by their respective IC 50 values of 17.81 ± 1.25 μM and 13.32 ± 0.84 μM. The discovery of these new compounds adds to the existing knowledge of A. tataricus 's chemical composition and potential applications. [Display omitted] [ABSTRACT FROM AUTHOR]

The monoterpene (+)-3-carene is associated with resistance of Sitka spruce against white pine weevil, a major North American forest insect pest of pine and spruce. High and low levels of (+)-3-carene in, respectively, resistant and susceptible Sitka spruce genotypes are due to variation of (+)-3-carene synthase gene copy number, transcript and protein expression levels, enzyme product profiles, and enzyme catalytic efficiency. A family of multiproduct (+)-3-carene synthase-like genes of Sitka spruce include the three (+)-3-carene synthases, PsTPS-3car1, PsTPS-3car2, PsTPS-3car3, and the (-)-sabinene synthase PsTPS-sab. Of these, PsTPS-3car2 is responsible for the relatively higher levels of (+)-3-carene in weevil-resistant trees. Here, we identified features of the PsTPS-3car1, PsTPS-3car2, PsTPS-3car3, and PsTPS-sab proteins that determine different product profiles. A series of domain swap and site-directed mutations, supported by structural comparisons, identified the amino acid in position 596 as critical for product profiles dominated by (+)-3-carene in PsTPS-3car1, PsTPS-3car2, and PsTPS-3car3, or (-)-sabinene in PsTPS-sab. A leucine in this position promotes formation of (+)-3-carene, whereas phenylalanine promotes (-)-sabinene. Homology modeling predicts that position 596 directs product profiles through differential stabilization of the reaction intermediate. Kinetic analysis revealed position 596 also plays a role in catalytic efficiency. Mutations of position 596 with different side chain properties resulted in a series of enzymes with different product profiles, further highlighting the inherent plasticity and potential for evolution of alternative product profiles of these monoterpene synthases of conifer defense against insects.

The structure of the title compound, C32H51NO6, was determined from 62-year-old crystals at room temperature and refined with 100 K data in a monoclinic (C2) space group. This compound with a triterpenoid structure, now confirmed by this study, played an important role in the determination of the structure of lanosterol. The molecules pack in linear O—H...O hydrogen-bonded chains along the short axis (b), while parallel chains display weak van der Waals interactions that explain the needle-shaped crystal morphology. The structure exhibits disorder of the flexible methylheptane chain at one end of the main molecule with a small void around it. Crystals of the compounds were resistant to data collection for decades with the available cameras and Mo Kα radiation single-crystal diffractometer in our laboratory until a new instrument with Cu Kα radiation operating at 100 K allowed the structure to be solved and refined.

Abstract Liphagal, isolated from the marine sponge Aka coralliphaga, exhibits phosphatidylinositol 3‐kinase alpha (PI3Kα) inhibitory activity and cytotoxic effects in human cancer cells. Siphonodictyal B, the biogenetic precursor of liphagal, also has PI3K inhibitory activity. However, its cytotoxic or antitumor activities have not been evaluated. In this study, we demonstrated that siphonodictyal B inhibits several kinases such as CDK4/6, CDK7, and PIM2 in addition to PI3K in vitro and that siphonodictyal B exhibits more potent cytotoxic effects than liphagal against human colon cancer cell lines. Furthermore, treatment with siphonodictyal B resulted in increased PARP cleavage, a larger sub‐G1 fraction, and a larger annexin V‐positive cell population, all of which are indicative of apoptosis induction. As a mechanism of apoptosis induction, we found that siphonodictyal B activates the p38 MAPK pathway, leading the upregulation of proapoptotic factors. Moreover, siphonodictyal B increased ROS levels, thus promoting p38 MAPK pathway activation. NAC, an ROS scavenger, almost completely reversed both the cytotoxic and p38 MAPK pathway‐activating effects of siphonodictyal B. These results indicate that the p38 MAPK pathway might be involved downstream of ROS signaling as part of the mechanism of siphonodictyal B‐induced apoptosis. Finally, siphonodictyal B displayed antitumor effects in a human colon cancer xenograft mouse model and increased p38 phosphorylation in tumor tissue. These results suggest that siphonodictyal B could serve as the basis of a novel anticancer drug.

Ferula assafoetida is a medicinal plant of the Apiaceae family that has traditionally been used for its therapeutic value. Particularly, terpenoid and phenylpropanoid metabolites, major components of the root-derived oleo-gum-resin, exhibit anti-inflammatory and cytotoxic activities, thus offering a resource for potential therapeutic lead compounds. However, genes and enzymes for terpenoid and coumarin-type phenylpropanoid metabolism have thus far remained uncharacterized in F. assafoetida. Comparative de novo transcriptome analysis of roots, leaves, stems, and flowers was combined with computational annotation to identify candidate genes with probable roles in terpenoid and coumarin biosynthesis. Gene network analysis showed a high abundance of predicted terpenoid- and phenylpropanoid-metabolic pathway genes in flowers. These findings offer a deeper insight into natural product biosynthesis in F. assafoetida and provide genomic resources for exploiting the medicinal potential of this rare plant.

Abstract Terpenoids are a group of largest natural products with important biological functions, and their efficient biosynthesis is of particular importance to both academia and industry. As the building blocks for terpenoid biosynthesis, a suitable supply of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is extremely crucial for efficient terpenoid biosynthesis. With this focus, we first introduce biosynthetic pathways of IPP and DMAPP, and then summarize the current strategies adopted for manipulating IPP and DMAPP supply. At last, how to further manage IPP and DMAPP supply to improve terpenoid biosynthesis is also proposed.

Terpenoids are the most diverse class of plant primary and specialized metabolites, and trans-prenyltransferases (trans-PTs) are the first branch point to synthesize precursors of various chain lengths for further metabolism. Whereas the catalytic mechanism of the enzyme is known, there is no reliable method for precisely predicting the functions of trans-PTs. With the exponentially increasing number of available trans-PTs genes in public databases, an in silico functional prediction method for this gene family is urgently needed. Here, we present PTS-Pre, a web tool developed on the basis of the “three floors” model, which shows an overall 86% prediction accuracy for 141 experimentally determined trans-PTs. The method was further validated by in vitro enzyme assays for randomly selected trans-PTs. In addition, using this method, we identified nine new GFPPSs from different plants which are beyond the previously reported Brassicaceae clade, suggesting these genes may have occurred via convergent evolution and are more likely lineage-specific. The high accuracy of our blind prediction validated by enzymatic assays suggests that PTS-Pre provides a convenient and reliable method for genome-wide functional prediction of trans-PTs enzymes and will surely benefit the elucidation and metabolic engineering of terpenoid biosynthetic pathways.

Dendrobium officinale is a kind of traditional Chinese herbal medicine. Its flowers could be used as health care tea for its aroma flavor and medicinal value. Most recent studies demonstrated that terpenoids are the main components of the aromatic compounds in the flowers, but the biosynthesis of terpenoids is poorly understood in D. officinale. In the experiment, the flowers from two cultivars of D. officinale with different smells were collected. The transcriptome analysis and combined volatile terpenoids determination were performed to identify the genes related to the biosynthesis of the terpenoids. The results showed that the different products of volatile terpenoids are α-thujene, linalool, α-terpineol, α-phellandrene, γ-muurolene, α-patchoulene, and δ-elemene in two cultivar flowers. The transcriptome analysis detected 25,484 genes in the flowers. And 18,650 differentially expressed genes were identified between the two cultivars. Of these genes, 253 genes were mapped to the terpenoid metabolism pathway. Among these genes, 13 terpene synthase (TPS) genes may have correlations with AP2/ERF, WRKY, MYB, bHLH, and bZIP transcription factors by weighted gene co-expression network analysis (WGCNA). The transcription factors have regulatory effects on TPS genes. These results may provide ideas for the terpenoid biosynthesis and regulatory network of D. officinale flowers.

Disease lesion mimic (Les / les) mutants display disease-like spontaneous lesions in the absence of pathogen infection, implying the constitutive activation of defense responses. However, the genetic and biochemical bases underlying the activated defense responses in those mutants remain largely unknown. Here, we performed integrated transcriptomics and metabolomics analysis on three typical maize Les mutants Les4 , Les10 , and Les17 with large, medium, and small lesion size, respectively, thereby dissecting the activated defense responses at the transcriptional and metabolomic level. A total of 1,714, 4,887, and 1,625 differentially expressed genes (DEGs) were identified in Les4 , Les10 , and Les17 , respectively. Among them, 570, 3,299, and 447 specific differentially expressed genes (SGs) were identified, implying a specific function of each LES gene. In addition, 480 common differentially expressed genes (CGs) and 42 common differentially accumulated metabolites (CMs) were identified in all Les mutants, suggesting the robust activation of shared signaling pathways. Intriguingly, substantial analysis of the CGs indicated that genes involved in the programmed cell death, defense responses, and phenylpropanoid and terpenoid biosynthesis were most commonly activated. Genes involved in photosynthetic biosynthesis, however, were generally repressed. Consistently, the dominant CMs identified were phenylpropanoids and flavonoids. In particular, lignin, the phenylpropanoid-based polymer, was significantly increased in all three mutants. These data collectively imply that transcriptional activation of defense-related gene expression; increase of phenylpropanoid, lignin, flavonoid, and terpenoid biosynthesis; and inhibition of photosynthesis are generalnatures associated with the lesion formation and constitutively activated defense responses in those mutants. Further studies on the identified SGs and CGs will shed new light on the function of each LES gene as well as the regulatory network of defense responses in maize. [ABSTRACT FROM AUTHOR]

Salvia miltiorrhiza is one of the most well known species in the genus Salvia of the Lamiaceae with great economic, academic and medicinal value. It was recorded as a traditional Chinese medicine material first in about the second century BC and later in many other ancient books. Salvia miltiorrhiza can be clinically used alone or mixed with other herbs to treat heart and cardiovascular diseases and is beneficial for management of many other diseases. In the last 30 years, S. miltiorrhiza has been studied intensively as a model system for medicinal plant biology. With the available of whole genome sequence of four S. miltiorrhiza lines and a large number of transcriptome, sRNAome and metabolome data, great progresses have been made in biosynthesis and regulatory mechanisms of bioactive compounds, such as tanshinones, phenolic acids, flavonoids, and prenylquinones. In this review, the recent results in the biosynthetic pathways of bioactive compounds in S. miltiorrhiza were summarized. The effects of biotic and abtiotic factors, plant hormones, transcription factors and noncoding RNAs on bioactive compound biosynthesis were overviewed. The mechanism of cross-talk and coordination among different biosynthetic pathways and the progress of metabolic engineering and synthetic biology for various bioactive compounds are also reviewed and discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Research into environmentally friendly alternatives to conventional plant protection products, to promote sustainable agriculture and healthy food, is strongly encouraged. RESULTS: In this context, 20 naturally occurring terpenoids and phenolic compounds were selected and evaluated in vitro as crop protection compounds against Zymoseptoria tritici, the causal agent of Septoria tritici blotch of wheat. After selection of the most active compounds, some hemisynthetic modifications were conducted to modify their lipophilicity. These modifications led to the discovery of sesamol esters as promising antifungal agents, with IC50 around 10 μg/mL and a total absence of cytotoxicity against human cells. CONCLUSION: These sesamol‐based derivatives should be selected for further evaluations in planta to validate their use as wheat crop protection agents. Moreover, the importance of a balanced hydrophily/lipophilicity ratio should be further studied. © 2021 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Dendrobium officinale is a kind of traditional Chinese herbal medicine. Its flowers could be used as health care tea for its aroma flavor and medicinal value. Most recent studies demonstrated that terpenoids are the main components of the aromatic compounds in the flowers, but the biosynthesis of terpenoids is poorly understood in D. officinale. In the experiment, the flowers from two cultivars of D. officinale with different smells were collected. The transcriptome analysis and combined volatile terpenoids determination were performed to identify the genes related to the biosynthesis of the terpenoids. The results showed that the different products of volatile terpenoids are α-thujene, linalool, α-terpineol, α-phellandrene, γ-muurolene, α-patchoulene, and δ-elemene in two cultivar flowers. The transcriptome analysis detected 25,484 genes in the flowers. And 18,650 differentially expressed genes were identified between the two cultivars. Of these genes, 253 genes were mapped to the terpenoid metabolism pathway. Among these genes, 13 terpene synthase (TPS) genes may have correlations with AP2/ERF, WRKY, MYB, bHLH, and bZIP transcription factors by weighted gene co-expression network analysis (WGCNA). The transcription factors have regulatory effects on TPS genes. These results may provide ideas for the terpenoid biosynthesis and regulatory network of D. officinale flowers. [ABSTRACT FROM AUTHOR]

This review highlights the application of intramolecular Heck reaction in total synthesis of natural products which were successfully synthesized in recent years (2013 to 2019). Heck cyclization was used as one of the strategic steps for constructions of wide variety of cyclic scaffolds essential for preparation of different natural products. [ABSTRACT FROM AUTHOR]

Terpenoids are one of the largest classes of natural products whose members possess a wide variety of biological activities. With several exceptions, scalable production of complex terpenoids with either purely biological or chemical methods still remains a major challenge. However, recent efforts to combine the two approaches in chemoenzymatic synthesis hold tremendous promise to address this challenge. Central to this paradigm is the development of useful biocatalytic methods, such as regioselective C-H oxidation, for terpene modifications. This review highlights recent applications of biocatalytic hydroxylation for site-selective modification of terpenoids. [ABSTRACT FROM AUTHOR]

Terpene synthase (TPS) gene family is ubiquitous in land plants and plays an important role in regulating various biological processes in plants, especially in pathogen and herbivore defense mechanisms. Also, little is known about this gene family in wheat. In this research, 153 TaTPS genes were identified and named according to their chromosome location. Phylogenetic analysis of TaTPS proteins and other homologous proteins corresponded to a six-subgroup classification. The analysis of gene structure and motif showed that the TaTPS gene was highly conserved in each subgroup, which suggested that whole genome duplication and segmental duplication events were the main expansion way of the TaTPS gene family. Nineteen tandem duplication gene pairs and 91 homologous genes on different chromosomes were produced by segmental duplication. Expression profiles derived from transcriptome data results indicated that TaTPS genes may contribute to defense responses of wheat to pests such as aphids. The cis-regulatory elements (CREs) of TaTPS were found to be diversified indicating that TaTPS gene may participate in many physiological processes of wheat growth and development. Each TaTPS gene contains at least two or more defense or hormone-related CREs, suggesting an important role in wheat pest defense through hormone pathways. This study can provide valuable clues for elucidating the evolutionary relationship of the TaTPS gene family. Also, it may provide a research basis for functional investigations related to wheat development, particularly to plant–pest interactions and further breeding for new wheat varieties with aphid resistance. [ABSTRACT FROM AUTHOR]

Amorpha‐4,11‐diene (AMD4,11) is a precursor to artemisinin, a potent antimalarial drug that is traditionally extracted from the shrubs of Artemisia annua. Despite significant prior efforts to produce artemisinin and its precursors through biotechnology, there remains a dire need for more efficient biosynthetic routes for its production. Here, we describe the optimization of key process conditions for an Escherichia coli strain producing AMD4,11 via the native methylerythritol phosphate (MEP) pathway. By studying the interplay between glucose uptake rates and oxygen demand, we were able to identify optimal conditions for increasing carbon flux through the MEP pathway by manipulating the availability of NADPH required for terpenoid production. Installation of an optimal qO2/qglucose led to a 6.7‐fold increase in product titers and a 6.5‐fold increase in carbon yield. [ABSTRACT FROM AUTHOR]

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019, resulting in the coronavirus disease-19 (COVID-19) pandemic. Coronaviruses are solely accountable for rising mortality and socioeconomic saddles. Presently, there are few repurposed drugs such as remdesivir or favipiravir approved for the treatment of COVID-19, although vaccines and plasma therapy is also subject to emergency approval. However, some potential natural treatments and cures have also been proposed. Molecules of natural origin showed therapeutic importance such as antiviral, anti-inflammatory, and antioxidant activity, and could be useful drug candidates for treating COVID-19. In recent years, essential oils have shown promising therapeutic effects against many viral diseases. Carvacrol is one of the monoterpene phenol with abundant presence in essential oils of many aromatic plants, including thyme and oregano. It is being used as food flavoring, additive, and preservatives. Carvacrol is also used as a fragrance in cosmetic products. A number of research studies have shown biological actions of carvacrol with its therapeutic potential is of clinical significance. The in vitro and in vivo studies have shown multiple pharmacological properties such as anticancer, anti-fungal, anti-bacterial, anti-oxidant, anti-inflammatory, vasorelaxant, hepatoprotective, and spasmolytic. This review highlights the various biological and pharmacological properties of carvacrol within the scope of COVID-19.

Plants thrive under abiotic and biotic stress conditions with the changes in phytohormones like salicylic acid (SA), resulting in the synthesis of secondary metabolites. The present study determines the response of plants in producing secondary metabolites towards different SA concentrations at varying time intervals. Liquid chromatography-mass spectrometry-based metabolomics studies in Aphanamixis polystachya (Wall.) Parker seedlings are grown at 10 mM, 50 mM, and 100 mM SA concentrations, showed the differential expression of metabolites towards the stress. Alkaloids like amaranthin showed a 15-fold increase on the second day, and analog of androvinblastin showed a 20-fold increase on the sixth day in 10 mM SA compared with other groups. Flavanoid cyanidin 3-3 glucosyl was found to be with a 22-fold increment along with terpenoids betavulgaroside (18-fold), asiaticoside (17-fold), mubenin B (20-fold), and deslanoside (22-fold) increment in 50 mM SA on the sixth day. The shock exerted by 100 mM was too harsh, and the lowered metabolite production level was insufficient for the seedlings to survive at this higher SA condition. Arrangement of stressed groups using Pearson correlation studies, principal component analysis, and partial least square analysis placed 10 mM SA and controlled group closer and 50 mM SA and 100 mM SA groups closer to each other. The study observed that SA regulates metabolites that mediate biotic stress responses at low concentrations, and higher concentrations regulate abiotic stress regulating metabolites.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019, resulting in the coronavirus disease-19 (COVID-19) pandemic. Coronaviruses are solely accountable for rising mortality and socioeconomic saddles. Presently, there are few repurposed drugs such as remdesivir or favipiravir approved for the treatment of COVID-19, although vaccines and plasma therapy is also subject to emergency approval. However, some potential natural treatments and cures have also been proposed. Molecules of natural origin showed therapeutic importance such as antiviral, anti-inflammatory, and antioxidant activity, and could be useful drug candidates for treating COVID-19. In recent years, essential oils have shown promising therapeutic effects against many viral diseases. Carvacrol is one of the monoterpene phenol with abundant presence in essential oils of many aromatic plants, including thyme and oregano. It is being used as food flavoring, additive, and preservatives. Carvacrol is also used as a fragrance in cosmetic products. A number of research studies have shown biological actions of carvacrol with its therapeutic potential is of clinical significance. The in vitro and in vivo studies have shown multiple pharmacological properties such as anticancer, anti-fungal, anti-bacterial, anti-oxidant, anti-inflammatory, vasorelaxant, hepatoprotective, and spasmolytic. This review highlights the various biological and pharmacological properties of carvacrol within the scope of COVID-19. [ABSTRACT FROM AUTHOR]

BACKGROUND Symptoms of pine wilt disease (PWD) are caused when pathogenic pine wood nematodes (PWN) invade healthy host trees via wounds created by adult Monochamus alternatus. Exogenous methyl jasmonate (MeJA) can trigger terpene‐based induced defense in conifers, which is a core part of the conifer defense system. Herein, we hypothesized that the terpene‐based plant defense induced by MeJA could negatively affect the feeding behavior of M. alternatus adults, and may contribute to a new strategy in the control of PWD. RESULTS: The feeding area for M. alternatus adults feeding on MeJA‐treated seedlings was significantly smaller compared with control seedlings. However, no significant difference was detected in the enzyme activities in the midgut of beetles that had fed on these seedlings. Terpenoids were mainly accumulated in traumatic resin duct, whereas the constitutive resin duct accumulated only diterpenoids. Correspondingly, large‐scaled responses at the transcriptional level mainly focused on terpenoid and phenolic biosynthesis in the defending trees. CONCLUSIONS: Breeding tree species with a high resin yield may contribute to control of the spread of PWD by suppressing the feeding of M. alternatus adults. Transcriptome sequencing results provided abundant information for further breeding of highly resistant trees. Based on these findings, a potential push–pull strategy for the control of M. alternatus was discussed. [ABSTRACT FROM AUTHOR]

Isoprenoids, also known as terpenes or terpenoids, represent a large family of natural products composed of five‐carbon isopentenyl diphosphate or its isomer dimethylallyl diphosphate as the building blocks. Isoprenoids are structurally and functionally diverse and include dolichols, steroid hormones, carotenoids, retinoids, aromatic metabolites, the isoprenoid side‐chain of ubiquinone, and isoprenoid attached signaling proteins. Productions of isoprenoids are catalyzed by a group of enzymes known as prenyltransferases, such as farnesyltransferases, geranylgeranyltransferases, terpenoid cyclase, squalene synthase, aromatic prenyltransferase, and cis‐ and trans‐prenyltransferases. Because these enzymes are key in cellular processes and metabolic pathways, they are expected to be potential targets in new drug discovery. In this review, six distinct subsets of characterized prenyltransferases are structurally and mechanistically classified, including (1) head‐to‐tail prenyl synthase, (2) head‐to‐head prenyl synthase, (3) head‐to‐middle prenyl synthase, (4) terpenoid cyclase, (5) aromatic prenyltransferase, and (6) protein prenylation. Inhibitors of those enzymes for potential therapies against several diseases are discussed. Lastly, recent results on the structures of integral membrane enzyme, undecaprenyl pyrophosphate phosphatase, are also discussed. [ABSTRACT FROM AUTHOR]

Melleolides and armillyl orsellinates are protoilludene-type aryl esters that are synthesized exclusively by parasitic fungi of the globally distributed genus Armillaria (Agaricomycetes, Physalacriaceae). Several of these compounds show potent antimicrobial and cytotoxic activities, making them promising leads for the development of new antibiotics or drugs for the treatment of cancer. We recently cloned and characterized the Armillaria gallica gene Pro1 encoding protoilludene synthase, a sesquiterpene cyclase catalyzing the pathway-committing step to all protoilludene-type aryl esters. Fungal enzymes representing secondary metabolic pathways are sometimes encoded by gene clusters, so we hypothesized that the missing steps in the pathway to melleolides and armillyl orsellinates might be identified by cloning the genes surrounding Pro1. Here we report the isolation of an A. gallica gene cluster encoding protoilludene synthase and four cytochrome P450 monooxygenases. Heterologous expression and functional analysis resulted in the identification of protoilludene-8α-hydroxylase, which catalyzes the first committed step in the armillyl orsellinate pathway. This confirms that ∆-6-protoilludene is a precursor for the synthesis of both melleolides and armillyl orsellinates, but the two pathways already branch at the level of the first oxygenation step. Our results provide insight into the synthesis of these valuable natural products and pave the way for their production by metabolic engineering. Key points: • Protoilludene-type aryl esters are bioactive metabolites produced by Armillaria spp. • The pathway-committing step to these compounds is catalyzed by protoilludene synthase. • We characterized CYP-type enzymes in the cluster and identified novel intermediates. [ABSTRACT FROM AUTHOR]

Terpenoids are one of the largest class of natural products with diverse structures and activities. This enormous diversity is embedded in enzymes called terpene synthases (TSs), which generate diverse terpene skeletons via sophisticated cyclization cascades. In addition to the many highly selective TSs, there are many promiscuous TSs that accept multiple prenyl substrates, or even noncanonical ones, with 6, 7, 8, 11, and 16 carbon atoms, synthesized via chemical approaches, C -methyltransferases, or engineered lepidopteran mevalonate pathways. The substrate promiscuity of TSs not only expands the structural diversity of terpenes but also highlights their potential for the discovery of novel terpenoids via combinatorial biosynthesis. In this review, we focus on the current knowledge on multisubstrate terpene synthases (MSTSs) and highlight their potential applications., (Copyright © 2024, Li and Tao.)

Cyanobacteria are attractive hosts for photosynthetic terpenoid production, using CO 2 as the sole carbon source. Although the methylerythritol phosphate (MEP) pathway is superior to the mevalonate pathway for cyanobacterial terpenoid synthesis, the first reaction of the MEP pathway, which is catalyzed by 1-deoxy-d-xylulose-5-phosphate (DXP) synthase, involves complex regulation and carbon loss. Here, we constructed a direct route linking ribulose-5-phosphate (Ru5P) in the Calvin-Benson (CB) cycle with DXP in the MEP pathway in a cyanobacterium to increase the terpenoid yield from CO 2 and bypass the DXS-targeted regulations. By employing the adaptive laboratory evolution, we identified new RibB variants including RibB 90-92del with a high activity of synthesizing DXP from Ru5P. These RibB variants were introduced into Synechococcus elongatus , resulting in the significantly increased photosynthetic production of isopentenol. The 13 C tracer experiments demonstrated a direct carbon flow from Ru5P in the CB cycle to the MEP pathway; thus, this direct route was denoted as the Ru5P shunt. The strain harboring the Ru5P shunt produced 105.2 mg L -1 of isopentenol with an average rate of 17.5 mg L -1 d -1 under continuous light conditions, which is higher than those ever reported for five-carbon alcohol production by photoautotrophic microorganisms. Utilization of the Ru5P shunt in cyanobacterial cells also improved the pinene production, which demonstrates that this shunt can be used to enhance the photosynthetic production of diverse terpenoids.

Seaweeds are a treasure trove of natural secondary metabolites. Terpenoids extracted from seaweeds are shown to possess a variety of antitumor cellular activities. However, due to the complex and diverse structures of terpenoids, their therapeutic targets and complex mechanisms of action have not been clarified. The present study summarises the research on terpenoids from seaweeds in oncological diseases over the last 20 years. Terpenoids show different degrees of inhibitory effects on different types of tumor cells, suggesting that terpenoids in seaweeds may have potential antitumor disease potential. Terpenoids with potential antitumor activity and their mechanism of action are investigated using network pharmacology. A total of 125 terpenoids and 286 targets are obtained. Proto-oncogene tyrosine-protein kinase Src(SRC), Signal transducer and activator of transcription 3 (STAT3), Mitogen-activated protein kinase (MAPK3, MAPK1), Heat shock protein HSP 90-alpha (HSP90AA1), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and RAC-alpha serine/threonine-protein kinase (AKT1) are defined as core targets. According to GO function and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis, terpenoids may affect the Phoshatidylinositol 3'-kinase (PI3K)-Akt signaling pathway, Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, Prostate cancer, MAPK signaling pathway, and Proteoglycans in cancer. In addition, the molecular docking results show that the selected terpenoids are all able to bind strongly to the active protein. Terpenoids may slow down the progression of cancer by controlling apoptosis, proliferation, and protein and enzyme binding., (© 2023 Wiley-VCH GmbH.)

Andrographolide, a naturally occurring trihydroxy diterpenoid, was extracted from the leaves of Andrographis paniculata. The molecule spontaneously formed vesicular self‐assemblies in aqueous binary liquid mixtures such as DMSO‐water (1 : 2), THF‐water (1 : 2), DMF‐water (1 : 2) and cyclohexanol‐water (2 : 1). The characterizations of the vesicular self‐assemblies were carried out by optical, atomic force and electron microscopic techniques, x‐ray diffraction and FTIR studies. The encapsulation of anionic fluorophore carboxyfluorescein and the cationic fluorophores rhodamine B and anti‐cancer drug doxorubicin by the self‐assemblies of andrographolide was also demonstrated. The entrapped drug molecules were released on treatment with the vesicle‐rupturing agent Triton X‐100. [ABSTRACT FROM AUTHOR]

Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids. [ABSTRACT FROM AUTHOR]

The root of Phlomis umbrosa has traditionally been used as a medicine in South Asian nations to treat colds and bone fractures, to staunch bleeding, and as an anti-inflammatory, and such use continues today. We identified 10 genes that are involved in terpenoid biosynthesis, while using the Illumina/Solexa HiSeq2000 platform. We investigated the transcript levels of the 10 genes using quantitative real-time PCR and quantified the level of terpenoid accumulation in different organs of P. umbrosa while using high-performance liquid chromatography. The transcript levels of PuHDR and PuHMGRl were the highest among the studied genes. Sesamoside, an iridoid glycoside, appeared in higher quantity than shanzhiside methylester, umbroside (8-O-acetyl shanzhiside methyl ester), and acteoside. We speculate that PuHDR and PuHMGR1 may contribute to terpenoid biosynthesis in P. umbrosa. This study highlights the molecular mechanisms that underlie iridoid glycoside biosynthesis in P. umbrosa. [ABSTRACT FROM AUTHOR]

2-Propyl-N′-[1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]pentanehydrazide was obtained in 80% yield via the Einhorn variation of the Schotten–Baumann method by (+)-camphor hydrazide condensation with valproic acid (VPA) chloride. The structure of the titled compound was verified by Raman, FTIR, 1H-NMR, and 13C-NMR spectral analysis along with FAB-mass spectrometry. Thermal properties of synthesized derivative were elucidated by DSC and its purity by HPLC. The compound was successfully tested as a potential anticonvulsant agent based on models of chemically- and electrically-induced seizures.

The entourage effect was a proposed explanation for biological observations that endocannabinoid ligand activities can be modified by other lipids released from cells at the same time. An increasing volume of anecdotal reports and interest in the plant have provoked research into the activity of minor chemical constituents of the plant—including volatile terpenoids such as myrcene, α- and β- pinene, β-caryophyllene, and limonene. However, to date, no clear interaction has been identified. The current study was designed to determine whether terpenes in the cannabis plant have detectable receptor-mediated activity, or modify the activity of Δ9-tetrahydrocannabinol, cannabidiol, or the endocannabinoid 2-arachidonylglycerol at the cannabinoid receptors. In addition, we have utilized a standard radioligand binding paradigm with ability to detect orthosteric and allosteric interactions of test compounds. With the possible exception of a weak interaction of β-caryophyllene with CB2, no data were produced to support the hypothesis that any of the five terpenes tested (either alone or in mixtures) have direct interactions with CB1 or CB2, as the binding of radioligand ([3H]-CP55,940), Δ9-tetrahydrocannabinol, and cannabidiol were unaltered by the presence of terpenes. Similarly, terpene functional effects were also not detected, either alone or in combination with Δ9-tetrahydrocannabinol, cannabidiol, or 2-arachidonoylglycerol. This study adds to the evidence that the putative entourage effect cannot be explained by direct effects at CB1 or CB2.

Abstract Background Recent advances in metabolic engineering enable the production of chemicals from sugars through microbial bio-conversion. Terpenes have attracted substantial attention due to their relatively high prices and wide applications in different industries. To this end, we synthesize and assess processes for microbial production of terpenes. Results To explain a counterintuitive experimental phenomenon where terpenes such as limonene (normal boiling point 176 °C) are often found to be 100% present in the vapor phase after bio-conversion (operating at only ~ 30 °C), we first analyze the vapor–liquid equilibrium for systems containing terpenes. Then, we propose alternative production configurations, which are further studied, using limonene as an example, in several case studies. Next, we perform economic assessment of the alternative processes and identify the major cost components. Finally, we extend the assessment to account for different process parameters, terpene products, ways to address terpene toxicity (microbial engineering vs. solvent use), and cellulosic biomass as a feedstock. We identify the key cost drivers to be (1) feed glucose concentration (wt%), (2) product yield (% of maximum theoretical yield) and (3) VVM (Volume of air per Volume of broth liquid per Minute, i.e., aeration rate in min−1). The production of limonene, based on current experimental data, is found to be economically infeasible (production cost ~ 465 $/kg vs. market selling price ~ 7 $/kg), but higher glucose concentration and yield can lower the cost. Among 12 terpenes studied, limonene appears to be the most reasonable short-term target because of its large market size (~ 160 million $/year in the US) and the relatively easier to achieve break-even yield (~ 30%, assuming a 14 wt% feed glucose concentration and 0.1 min−1 VVM). Conclusions The methods proposed in this work are applicable to a range of terpenes as well as other extracellular insoluble chemicals with density lower than that of water, such as fatty acids. The results provide guidance for future research in metabolic engineering toward terpenes production in terms of setting targets for key design parameters.

Abstract Background β-Ionone is a fragrant terpenoid that generates a pleasant floral scent and is used in diverse applications as a cosmetic and flavoring ingredient. A growing consumer desire for natural products has increased the market demand for natural β-ionone. To date, chemical extraction from plants remains the main approach for commercial natural β-ionone production. Unfortunately, changing climate and geopolitical issues can cause instability in the β-ionone supply chain. Microbial fermentation using generally recognized as safe (GRAS) yeast offers an alternative method for producing natural β-ionone. Yarrowia lipolytica is an attractive host due to its oleaginous nature, established genetic tools, and large intercellular pool size of acetyl-CoA (the terpenoid backbone precursor). Results A push–pull strategy via genome engineering was applied to a Y. lipolytica PO1f derived strain. Heterologous and native genes in the mevalonate pathway were overexpressed to push production to the terpenoid backbone geranylgeranyl pyrophosphate, while the carB and biofunction carRP genes from Mucor circinelloides were introduced to pull flux towards β-carotene (i.e., ionone precursor). Medium tests combined with machine learning based data analysis and 13C metabolite labeling investigated influential nutrients for the β-carotene strain that achieved > 2.5 g/L β-carotene in a rich medium. Further introduction of the carotenoid cleavage dioxygenase 1 (CCD1) from Osmanthus fragrans resulted in the β-ionone production. Utilization of in situ dodecane trapping avoided ionone loss from vaporization (with recovery efficiencies of ~ 76%) during fermentation operations, which resulted in titers of 68 mg/L β-ionone in shaking flasks and 380 mg/L in a 2 L fermenter. Both β-carotene medium tests and β-ionone fermentation outcomes indicated the last enzymatic step CCD1 (rather than acetyl-CoA supply) as the key bottleneck. Conclusions We engineered a GRAS Y. lipolytica platform for sustainable and economical production of the natural aroma β-ionone. Although β-carotene could be produced at high titers by Y. lipolytica, the synthesis of β-ionone was relatively poor, possibly due to low CCD1 activity and non-specific CCD1 cleavage of β-carotene. In addition, both β-carotene and β-ionone strains showed decreased performances after successive sub-cultures. For industrial application, β-ionone fermentation efforts should focus on both CCD enzyme engineering and strain stability improvement.

Twelve endophytic fungi were isolated from Jeruju plant. Three of which have the best antioxidant activity, namely Culvularia lunata DJS1, Diaporthe phaseolorum DJS2, and Colletotrichum siamense BJS4. The fungi can produce secondary metabolites that have the potential as antioxidant compounds. This study aims to isolate the antioxidant compound using a chromatography column and test the antioxidant activity using DPPH method. Isolation of secondary metabolites produced 40 eluates. The IC50 value of DJS111 and BJS42 eluates were 10.20 µg/ml and 20.89 µg/ml, which is an antioxidant compound with very strong activity. The IC50 value of DJS24 eluate was 54.45 µg/ml, which is strong antioxidant activity. DJS111 eluate has antioxidant activity that approaches to ascorbic acid as a standart antioxidant compound (7.76µg/ml). From TLC, DJS111 contains flavonoid compound and DJS24 and BJS42 contain terpenoid compound.

Abstract Background Dental caries remains a serious problem due to its detrimental effects on individual health and quality of life. The bulbs of Myrmecodia pendans (Merr & Perry), native plants of Papua, have been used as natural remedies for tumours, gout, diarrhoea, and fever. In this study, one of the active compounds of M. pendans was isolated, and its biological activity against the formation of Streptococcus mutans ATCC 25175 biofilm was tested. Methods M. pendans was extracted with ethyl acetate using a Soxhlet apparatus. The extract was then separated, and chromatographic purification provided the isolated compound. The structure of the active compound was then characterized using UV, IR, NMR, and MS spectrometry. The obtained compound was added to S. mutans biofilms to determine the MBIC and MBEC values. Results The compound isolated from M. pendans was determined to be a labdane diterpene derivative with the formula C31H50O3. The MBIC value of the terpenoid towards the S. mutans biofilms was 50 ppm, and the MBEC value for the 1 min induction time was 40%. Conclusion The terpenoid extracted from M. pendans has the potential to be developed into an antibacterial agent particularly for preventing the formation of biofilms.

Terpene synthases are widely distributed in Actinobacteria. Genome sequencing of Streptomyces sp. NRRL S-4 uncovered a biosynthetic gene cluster (BGC) that putatively synthesizes pentalenolactone type terpenes. Guided by genomic information, the S-4 strain was chemically investigated, resulting in the isolation of two new sesquiterpenoids, 1-deoxy-8α-hydroxypentalenic acid (1) and 1-deoxy-9β-hydroxy-11-oxopentalenic acid (2), as shunt metabolites of the pentalenolactone (3) biosynthesis pathway. Their structures and absolute configurations were elucidated by analyses of HRESIMS and NMR spectroscopic data as well as time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Compounds 1 and 2 exhibited moderate antimicrobial activities against Gram-positive and Gram-negative bacteria. These results confirmed that the pentalenolactone pathway was functional in this organism and will facilitate efforts for exploring Actinobacteria using further genome mining strategies.

Crop domestication and improvement often concurrently affect plant resistance to pests and production of secondary metabolites, creating challenges for isolating the ecological implications of selection for specific metabolites. Cucurbitacins are bitter triterpenoids with extreme phenotypic differences between Cucurbitaceae lineages, yet we lack integrated models of herbivore preference, cucurbitacin accumulation, and underlying genetic mechanisms. In Cucurbita pepo, we dissected the effect of cotyledon cucurbitacins on preference of a specialist insect pest (Acalymma vittatum) for multiple tissues, assessed genetic loci underlying cucurbitacin accumulation in diverse germplasm and a biparental F2 population (from a cross between two independent domesticates), and characterized quantitative associations between gene expression and metabolites during seedling development. Acalymma vittatum affinity for cotyledons is mediated by cucurbitacins, but other traits contribute to whole‐plant resistance. Cotyledon cucurbitacin accumulation was associated with population structure, and our genetic mapping identified a single locus, Bi‐4, containing genes relevant to transport and regulation – not biosynthesis – that diverged between lineages. These candidate genes were expressed during seedling development, most prominently a putative secondary metabolite transporter. Taken together, these findings support the testable hypothesis that breeding for plant resistance to insects involves targeting genes for regulation and transport of defensive metabolites, in addition to core biosynthesis genes. In domesticated Cucurbita pepo we found a novel genetic locus underlying spatial and temporal variation in cucurbitacin production, defensive metabolites that confer susceptibility to a specialized, cucurbitacin‐sequestering insect pest, Acalymma vittatum (Coleoptera: Chrysomelidae) [ABSTRACT FROM AUTHOR]

Copyright of Acta Edulis Fungi is the property of Acta Edulis Fungi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the present study, a GC‐MS method used for quantitative screening of 26 compounds (sclareolide, sclareol, ferruginol, cryptanol, 6,7‐dehydroroyleanone, suginal, 9,10‐dihydro‐7,8‐dimethyl‐2‐(1‐methylethyl) phenanthren‐3‐ol, sugiol, inuroyleanone, 12‐demethylmulticauline, 7α‐hydroxy‐β‐sitosterol, stigmasterol, sitosterol, salvigenin, sinensetin, α‐amyrin, lupeol, lupenone, 3‐acetyl lupeol, 1α,21α‐dihydroxy‐2,3‐(1′1′‐dimethyl‐dioxymethylene) urs‐9(11),12‐dien, uvaol, betulin, pyxinol, lup‐(20),29‐ene‐2α‐hydroxy‐3β‐acetate, betulin 3β, 28β‐diacetate, 21α‐hydroxy,2α,3β‐diacetoxy urs‐9(11),12‐dien) specific to Turkish Salvia species was developed and validated. According to the GC–MS analysis results, Salvia hypargeia Fisch. & C.A. Mey. roots were found to be rich in ferruginol (30787.97 µg/g extract) and lupenone (23276.21 µg/g extract), and leaves in lupeol (20625.92 µg/g extract). Additionally, the essential oil and aroma contents of this species were identified by GC‐MS technique. According to the LC‐MS/MS results, especially S. hypargeia leaf extract was rich in rosmarinic acid (38035.7 µg/g extract) and isoquercitrin (4136.91 µg/g extract). Furthermore, anticholinesterase, antiurease, antityrosinase and antielastase inhibitory, antioxidant, cytotoxic activities of the ethanol extracts, essential oil, and major components of the species were evaluated. Antioxidant potentials of all extracts of this species were quite high in all studied antioxidant methods. Moreover, butyrylcholinesterase and elastase inhibitory capacities of ferruginol, the major component of S. hypargeia roots, were notable. For these reasons, this species has a high potential for food and pharmaceutical industries. Practical applications: This new GC–MS method was applied to S. hypargeia Fisch. & C.A. Mey. and it indicated that this species possessed high amount of ferruginol and lupeol, and that this species could be used for their natural sources. According to the results of the activity studies (antioxidant, anticholinesterase, tyrosinase, elastase, and cytotoxic), this method was used to exhibit which compound may be responsible for the activities. This developed and validated method could be easily applied to determine major/active/toxic secondary metabolites of Salvia species which are used and/or could be used in pharmaceutical, cosmetic, and food industries. [ABSTRACT FROM AUTHOR]

The terpenoid (−)‐Istanbulin A is a natural product isolated from Senecio filaginoides DC, one of the 270 species of Senecio (Asteraceae) which occurs in Argentina. The structure and absolute configuration of this compound [9a‐hydroxy‐3,4a,5‐trimethyl‐4a,6,7,8a,9,9a‐hexahydro‐4H,5H‐naphtho[2,3‐b]‐furan‐2,8‐dione or (4S,5R,8R,10S)‐1‐oxo‐8β‐hydroxy‐10βH‐eremophil‐7(11)‐en‐12,8β‐olide, C15H20O4] were determined by single‐crystal X‐ray diffraction studies. It proved to be a sesquiterpene lactone showing an eremophilanolide skeleton whose chirality is described as 4S,5R,8R,10S. Structural results were also in agreement with the one‐ and two‐dimensional (1D and 2D) NMR and HR–ESI–MS data, and other complementary spectroscopic information. In addition, (−)‐Istanbulin A is a polymorph of the previously reported form of (−)‐Istanbulin A, form I; thus, the title compound is denoted form II or polymorph II. Structural data and a literature search allowed the chirality of Istanbulin A to be revisited. The antimicrobial and antifungal activities of (−)‐Istanbulin A, form II, were evaluated in order to establish a reference for future comparisons and applications related to specific crystal forms of Istanbulins. [ABSTRACT FROM AUTHOR]

Gedunin is a natural tetranorterpenoid secondary metabolite found in plants of the Meliaceae family, which has been reported for its antiparasitic, antifungal and anticancer activities. Here, we describe the molecular mechanisms underlying the in vitro anti proliferative activity of gedunin (isolated from the mangrove plant Xylocarpus granatum) in human ovarian cancer cells. We observed that gedunin triggered severe ROS generation leading to DNA damage and cell cycle arrest in G2/M phase thus inhibiting cell proliferation. ROS upregulation also led to mitochondrial stress and membrane depolarization, which eventually resulted in mitochondria-mediated apoptosis following cytochrome C release, caspase 9, 3 activation, and PARP cleavage. Transmission electron microscopy of gedunin treated cells revealed sub-cellular features typical of apoptosis. Moreover, an upregulation in stress kinases like phospho-ERK 1/2, phospho-p38 and phospho-JNK was also observed in gedunin treated cells. Free radical scavenger N-Acetyl-L-Cysteine (NAC) reversed all these effects resulting in increased cell survival, abrogation of cell cycle arrest, rescue of mitochondrial membrane potential and suppression of apoptotic markers. Interestingly, gedunin is also an inhibitor of the evolutionarily conserved molecular chaperone Heat Shock Protein 90 (hsp90) responsible for maintaining cellular homeostasis. Targeting this chaperone could be an attractive strategy for developing cancer therapeutics since many oncogenic proteins are also client proteins of hsp90. Collectively, our findings provide insights into the molecular mechanism of action of gedunin, which may aid drug development efforts against ovarian cancer. [ABSTRACT FROM AUTHOR]

Aim: Thyroid cancer is a commonly detected endocrine malignant tumour which accounts for 1% of the total human cancers. The present study was aimed to investigate the effect of apigetrin on anaplastic thyroid cancer cell viability and understand the mechanism involved. Materials and Methods: Fluorescent microscopy using diamidino-2- phenylindole (DAPI)staining was used to examine the nuclear fragmentation. Changes in protein expression were analysed by Western blot analysis and migration potential using wound healing assay. Results: Treatment with apigetrin exhibited inhibitory effect on anaplastic thyroid cancer cell viability in dose based manner. The cleavage of PARP and activation of caspase-3/-9 was promoted in anaplastic thyroid cancer cells on treatment with apigetrin. A significant reduction in hypoxiainducible factor1a (HIF1a) and vascular endothelial growth factor (VEGF) expression was caused by apigetrin in anaplastic thyroid cancer cells. The count of Terminal deoxynucleotidyltransferase-mediated nick end labeling (TUNEL)-positive cells was increased significantly (p<0.05) in the cell cultures on treatment with apigetrin. The cell migration was also suppressed by apigetrin in dose based manner. Moreover, treatment of mice with apigetrin inhibited the tumor growth and development markedly in comparison to the untreated group. Conclusion: The present study demonstrates that apigetrin plays an important role in the inhibition of thyroid cancer. Therefore, apigetrin needs to be investigated further as therapeutic agent for thyroid cancer treatment. [ABSTRACT FROM AUTHOR]

Six new compounds, including three terpenoids (1-3) and three lignans (4-6), were isolated from the 95% EtOH extract of the twigs of Tripterygium hypoglaucum. Their structures were determined on the basis of extensive spectroscopic analysis. 9′-O-benzoyl-lariciresinol (4) showed weak cytotoxicity against HepG2/Adr cells, with an IC50 value of 30.1 μM in vitro. [ABSTRACT FROM AUTHOR]

Recently, the research on conversion of biodiesel by-products to high value-added products has received much attention, due to the adverse effects of large accumulations of biodiesel by-products caused by the rapid increase in biodiesel production. Herein, this study investigated the utilization of by-products crude glycerol (CG-1 and CG-2) from two different industrial methods of biodiesel production and the favorable fermentation conditions for the high yield of β-farnesene by an engineered Escherichia coli F4, which harbored an optimized mevalonate pathway. Through analyzing by-products' components and fermentation performance, we found that CG-2 did not contain harmful impurities such as methanol and black solid impurities, and the β-farnesene production was up to 2.7 g/L from CG-2, which was similar to that from pure glycerol (2.5 g/L) and higher than that (2.21 g/L) from CG-1. Therefore, CG-2 was more suitable for β-farnesene production than CG-1, which might provide a reference for choosing a more suitable method on practical biodiesel production. Afterward, a variety of important fermentation conditions were explored using CG-2 as a substrate in shaken flasks. Under the optimal conditions (including induced cell density 1.0, initial cell density 0.25, temperature after induction 33 °C, initial medium pH 6.5), the yield of β-farnesene from CG-2 reached 10.31 g/L in a 5-L bioreactor, which was 2.8-fold higher than initial conditions in shake flasks and was the highest yield of β-farnesene produced from biodiesel by-products by fermentation as well. The recommended fermentation conditions in this work will provide a valuable reference for the industrial production of β-farnesene utilizing biodiesel by-products. [ABSTRACT FROM AUTHOR]

Incorporation of the Beckmann rearrangement into the presented research resulted in the formation of nitrogen-containing terpenoid derivatives originating from naturally occurring compounds. Both starting monoterpenes and obtained derivatives were subjected to estimation of their antibacterial potential. In the presented study, Staphylococcus aureus was the most sensitive to examined compounds. The Minimal Inhibitory Concentration (MIC) experiments performed on S. aureus demonstrated that the (−)-menthone oxime (−)-8 and (+)-pulegone oxime (+)-13 had the best antibacterial activity among the tested derivatives and starting compounds. Their MIC90 value was 100 µg/mL. The obtained derivatives were also evaluated for their inhibitory activity against bacterial urease. Among the tested compounds, three active inhibitors were found – oxime 14 and lactams (−)-15 and 16 limited the activity of Sporosarcina pasteurii urease with Ki values of 174.3 µM, 43.0 µM and 4.6 µM, respectively. To our knowledge, derivative 16 is the most active antiureolytic lactam described to date. [ABSTRACT FROM AUTHOR]

Plant metabolites being renewable in nature have tremendous significance for the development of a sustainable society. In this manuscript we show that, terpenoids having nanometric lengths, commonly having several functional groups and several centers of chirality, can be utilized as renewable Molecular Functional Nanos (MFNs). The terpenoids spontaneously self-assembled in liquids yielding different morphologies such as vesicles, tubes, flowers, petals and fibers of nano- to micro-meter dimensions and supramolecular gels. The self-assemblies were utilized for the entrapment and release of fluorophores including anticancer drug, pollutant capture, generation of hybrid materials and catalysis. [ABSTRACT FROM AUTHOR]

This paper introduce the advances in study of antibacterial effects of natural medicines in the past ten years. The antibacterial components of natural medicines mainly include flavonoids, terpenoids, alkaloids, lignans, phenols, etc.. This paper is intended to provide data reference for the research and development of new natural antibacterial medicines. [ABSTRACT FROM AUTHOR]

Copyright of Biotechnologie, Agronomie, Societe et Environnement is the property of Les Presses Agronomiques de Gembloux and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Allium sativum contain various medicinal properties like immunomodulatory, antitumorigenetic, antiatherosclerotic and antimicrobial. The endotoxin lipopolysaccharide (LPS) is a dominant component of the outer membranes of Gram-negative bacteria, which is largely responsible for toxic inflammatory reactions. The main objective of this study is isolation and structural elucidation of bioactive compound from Allium sativum and estimates its possible nephroprotective role in LPS intoxicated mice. Fresh bulbs of Allium sativum were collected and identified by a taxonomist. Bulbs were powdered and extracted by soxhlet 85% hydroethanol solvent. The extract was subjected to different chromatography techniques to isolate a novel bioactive compound whose structure was elucidated with the help of FTIR, NMR and LC-MS and determine the effect of hydroethanol extract of Allium sativum in LPS challenged mice. The structure of the isolated compound was elucidated as Terpenoid and its IUPAC name is Isopropyl 2-(3-acetyl-5-(3,3-dimethylbut-1-en-2-yl)phenyl)-4-isopropyl-3-methyleneheptanoate. Allium sativum significantly attenuated the LPS-induced renal toxicity. The present results provide evidence that hydroethanol extract of Allium sativum possess nephroprotective role and it provides protection from LPS induced nephrotoxicity. Thus is conclude that isolated compound contains nephroprotective activity against LPS induce nephrotoxicity in Swiss albino mice. [ABSTRACT FROM AUTHOR]