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1.
Gene ; 932: 148893, 2025 Jan 10.
Article in English | MEDLINE | ID: mdl-39197797

ABSTRACT

Flowers of Crocus sativus L. are immensely important not only for arrangement of floral whorls but more because each floral organ is dominated by a different class of specialized compounds. Dried stigmas of C. sativus flowers form commercial saffron, and are known to accumulate unique apocarotenoids like crocin, picrocrocin and safranal. Inspite of being a high value crop, the molecular mechanism regulating flower development in Crocus remains largely unknown. Moreover, it would be very interesting to explore any co-regulatory mechanism which controls floral architecture and secondary metabolic pathways which exist in specific floral organs. Here we report transcriptome wide identification of MADS box genes in Crocus. A total of 39 full length MADS box genes were identified among which three belonged to type I and 36 to type II class. Phylogeny classified them into 11 sub-clusters. Expression pattern revealed some stigma up-regulated genes among which CstMADS19 encoding an AGAMOUS gene showed high expression. Transient over-expression of CstMADS19 in stigmas of Crocus resulted in increased crocin by enhancing expression of pathway genes. Yeast one hybrid assay demonstrated that CstMADS19 binds to promoters of phytoene synthase and carotenoid cleavage dioxygenase 2 genes. Yeast two hybrid and BiFC assays confirmed interaction of CstMADS19 with CstMADS26 which codes for a SEPALATA gene. Co-overexpression of CstMADS19 and CstMADS26 in Crocus stigmas enhanced crocin content more than was observed when genes were expressed individually. Collectively, these findings indicate that CstMADS19 functions as a positive regulator of stigma based apocarotenoid biosynthesis in Crocus.


Subject(s)
Carotenoids , Crocus , Flowers , Gene Expression Regulation, Plant , MADS Domain Proteins , Plant Proteins , Crocus/genetics , Crocus/metabolism , Carotenoids/metabolism , Flowers/genetics , Flowers/metabolism , Flowers/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , MADS Domain Proteins/genetics , MADS Domain Proteins/metabolism , Phylogeny , Gene Expression Profiling/methods , Cyclohexenes/metabolism , Transcriptome , Terpenes/metabolism , Glucosides/metabolism , Glucosides/biosynthesis
2.
NPJ Syst Biol Appl ; 10(1): 109, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39353984

ABSTRACT

Engineered microorganisms have emerged as viable alternatives for limonene production. However, issues such as low enzyme abundance or activities, and regulatory feedback/forward inhibition may reduce yields. To understand the underlying metabolism, we adopted a systems biology approach for an engineered limonene-producing Escherichia coli strain K-12 MG1655. Firstly, we generated time-series metabolomics data and, secondly, developed a dynamic model based on enzyme dynamics to track the native metabolic networks and the engineered mevalonate pathway. After several iterations of model fitting with experimental profiles, which also included 13C-tracer studies, we performed in silico knockouts (KOs) of all enzymes to identify bottleneck(s) for optimal limonene yields. The simulations indicated that ALDH/ADH (aldehyde dehydrogenase/alcohol dehydrogenase) and LDH (lactate dehydrogenase) suppression, and HK (hexokinase) enhancement would increase limonene yields. Experimental confirmation was achieved, where ALDH-ADH and LDH KOs, and HK overexpression improved limonene yield by 8- to 11-fold. Our systems biology approach can guide microbial strain re-engineering for optimal target production.


Subject(s)
Escherichia coli , Limonene , Metabolic Engineering , Systems Biology , Limonene/metabolism , Systems Biology/methods , Escherichia coli/genetics , Escherichia coli/metabolism , Metabolic Engineering/methods , Metabolic Networks and Pathways/genetics , Metabolomics/methods , Computer Simulation , Terpenes/metabolism , Aldehyde Dehydrogenase/metabolism , Aldehyde Dehydrogenase/genetics , Models, Biological , Mevalonic Acid/metabolism
3.
Pharmacol Res Perspect ; 12(5): e70022, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39358913

ABSTRACT

Nephrotoxicity occurs when the body is exposed to certain drugs or toxins. When kidney damage occurs, the kidney fails to eliminate excess urine and waste. Solanesol (C45H74O) is a tri-sesquiterpenoid alcohol first isolated from tobacco, and it is widely distributed in plants of the Solanaceae family. Solanesol (SNL) is an intermediate in the synthesis of coenzyme Q10 (CoQ10), an antioxidant which protects nerve cells. This study investigated the protective effect of SNL at doses of 30 and 60 mg/kg in gentamicin-induced nephrotoxicity in Wistar albino rats. Animals were distributed into six groups and administered 100 mg/kg gentamicin-intraperitoneal injection for 14 days. Biochemical assessments were performed on kidney homogenate, blood, and serum. Treatment with SNL was shown as lower serum levels of creatinine, blood urea nitrogen (BUN), thiobarbituric acid reactive substances (TBARS), and Tumor necrosis factor alpha)TNF-α ((p < .001). It also restored reduced glutathione (GSH) and mitochondrial complex enzymatic activity as protective measures against gentamicin-induced nephrotoxicity. SNL were shown to reduce inflammation and oxidative stress markers (p < .001). Histological findings furtherly augmented the protective effects of SNL. Long-term SNL therapy also restored mitochondrial electron transport chain complex enzymes, such as complex-I (p < .001). In conclusion, these findings suggest that SNL can represent a protective therapeutic option for drug-induced nephrotoxicity, a long-term adverse effect of aminoglycoside antibiotics such as gentamicin.


Subject(s)
Gentamicins , Kidney , Oxidative Stress , Rats, Wistar , Ubiquinone , Gentamicins/toxicity , Animals , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquinone/therapeutic use , Rats , Oxidative Stress/drug effects , Male , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Antioxidants/pharmacology , Antioxidants/therapeutic use , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Kidney Diseases/prevention & control , Kidney Diseases/metabolism , Glutathione/metabolism , Creatinine/blood , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Blood Urea Nitrogen , Terpenes/pharmacology , Terpenes/therapeutic use , Thiobarbituric Acid Reactive Substances/metabolism , Anti-Bacterial Agents/toxicity
4.
Commun Biol ; 7(1): 1263, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39367037

ABSTRACT

Natural secondary metabolites are medically, agriculturally, and industrially beneficial to humans. For mass production, a heterologous production system is required, and various metabolic engineering trials have been reported in Escherichia coli and Saccharomyces cerevisiae to increase their production levels. Recently, filamentous fungi, especially Aspergillus oryzae, have been expected to be excellent hosts for the heterologous production of natural products; however, large-scale metabolic engineering has hardly been reported. Here, we elucidated candidate metabolic pathways to be modified for increased model terpene production by RNA-seq and metabolome analyses in A. oryzae and selected pathways such as ethanol fermentation, cytosolic acetyl-CoA production from citrate, and the mevalonate pathway. We performed metabolic modifications targeting these pathways using CRISPR/Cas9 genome editing and demonstrated their effectiveness in heterologous terpene production. Finally, a strain containing 13 metabolic modifications was generated, which showed enhanced heterologous production of pleuromutilin (8.5-fold), aphidicolin (65.6-fold), and ophiobolin C (28.5-fold) compared to the unmodified A. oryzae strain. Therefore, the strain generated by engineering multiple metabolic pathways can be employed as a versatile highly-producing host for a wide variety of terpenes.


Subject(s)
Aspergillus oryzae , Biological Products , Gene Editing , Metabolic Engineering , Metabolic Networks and Pathways , Metabolic Engineering/methods , Gene Editing/methods , Biological Products/metabolism , Aspergillus oryzae/genetics , Aspergillus oryzae/metabolism , Metabolic Networks and Pathways/genetics , CRISPR-Cas Systems , Terpenes/metabolism
5.
Science ; 386(6718): 167-175, 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39388539

ABSTRACT

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of >400 natural products with a broad spectrum of bioactivity, ranging from antidepressant and antimicrobial to anti-obesity and anticancer activity. Here, we present a scalable, regio-, site-, and enantioselective catalytic method for synthesis of cyclic ß-prenyl ketones, compounds that can be used for efficient syntheses of many PPAPs in high enantiomeric purity. The transformation is prenyl conjugate addition to cyclic ß-ketoesters promoted by a readily accessible chiral copper catalyst and involving an easy-to-prepare and isolable organoborate reagent. Reactions reach completion in just a few minutes at room temperature. The importance of this advance is highlighted by the enantioselective preparation of intermediates previously used to generate racemic PPAPs. We also present the enantioselective synthesis of nemorosonol (14 steps, 20% yield) and its one-step conversion to another PPAP, garcibracteatone (52% yield).


Subject(s)
Biological Products , Phloroglucinol , Biological Products/chemical synthesis , Biological Products/chemistry , Catalysis , Copper/chemistry , Ketones/chemistry , Neoprene , Phloroglucinol/chemistry , Phloroglucinol/chemical synthesis , Polycyclic Compounds/chemical synthesis , Polycyclic Compounds/chemistry , Prenylation , Stereoisomerism , Terpenes/chemical synthesis , Terpenes/chemistry
6.
Molecules ; 29(19)2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39407591

ABSTRACT

The root of Paeonia lactiflora pall. is a significant component of traditional Chinese medicine, with terpenoids and their glycosides, such as paeoniflorins, serving as key active ingredients known for their anti-inflammatory, hepatoprotective, and analgesic properties. By generating a transcriptome and functionally characterizing 32 terpene synthases (TPSs) from P. lactiflora, we successfully constructed 24 pESC-Trp-PlTPS expression vectors. Through expression in Saccharomyces cerevisiae engineered strains, we identified four mono-TPSs and five sesqui-TPSs that produce 18 compounds, including eight monoterpenes and ten sesquiterpenes in vitro. This includes a bifunctional enzyme (PlTPS22). Additionally, PlTPS21 was characterized as a pinene synthase with α-pinene as its main product. The expression pattern of PlTPS21 aligns closely with the accumulation patterns of paeoniflorins and α-pinene in the plant, suggesting that PlTPS21 is a key enzyme in the biosynthesis of paeoniflorin.


Subject(s)
Alkyl and Aryl Transferases , Paeonia , Paeonia/genetics , Paeonia/enzymology , Paeonia/metabolism , Alkyl and Aryl Transferases/genetics , Alkyl and Aryl Transferases/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Terpenes/metabolism , Terpenes/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Phylogeny , Transcriptome
7.
Molecules ; 29(19)2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39407647

ABSTRACT

Tricholoma are significant medicinal and edible mushrooms within Basidiomycota. Known for their various medicinal properties such as anti-tumor, immune regulation, and antioxidant effects, they are regarded worldwide as health foods of the 21st century. Tricholoma species produce various types of secondary metabolites, which have been extensively studied by the scientific community. In 2018, Clericuzio et al. summarized the structures, biosynthesis, and biological activities of over one hundred different secondary metabolites isolated from the fruiting bodies of 25 Tricholoma species. Building on this, the present article reviews the research progress on Tricholoma secondary metabolites from 2018 to 2023, identifying a total of 101 compounds, 46 of which were newly discovered. These secondary metabolites include a wide range of chemical categories such as terpenoids, steroids, and alkaloids, demonstrating broad biological activities. This article aims to provide in-depth scientific insights and guidance for researchers in this field by summarizing the chemical and biological properties of these secondary metabolites, promoting further applications and development of Tricholoma fungi in the pharmaceutical and food industries.


Subject(s)
Secondary Metabolism , Tricholoma , Tricholoma/chemistry , Terpenes/chemistry , Terpenes/metabolism , Humans , Biological Products/chemistry , Biological Products/pharmacology , Alkaloids/chemistry , Alkaloids/biosynthesis , Alkaloids/pharmacology , Fruiting Bodies, Fungal/chemistry , Fruiting Bodies, Fungal/metabolism , Steroids/chemistry , Steroids/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
8.
Molecules ; 29(19)2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39407682

ABSTRACT

Camellia luteoflora is a rare and endangered plant endemic to China. It has high ornamental and potential economic and medicinal value, and is an important germplasm resource of Camellia. To understand the distributions and differences in metabolites from different parts of C. luteoflora, in this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to examine the types and contents of chemical constituents in five organs of C. luteoflora: roots, stems, leaves, flowers, and fruits. The results showed that a total of 815 metabolites were identified in the five organs and were classified into 18 main categories, including terpenoids (17.1%), amino acids (10.4%), flavonoids (10.3%), sugars and alcohols (9.8%), organic acids (9.0%), lipids (7.1%), polyphenols (4.8%), alkaloids (4.8%), etc. A total of 684 differentially expressed metabolites (DEMs) in five organs were obtained and annotated into 217 KEGG metabolic pathways, among which metabolic pathways, ABC transporters, the biosynthesis of cofactors, and the biosynthesis of amino acids were significantly enriched. In DEMs, flowers are rich in flavonoids, polyphenols, organic acids, and steroids; fruits are rich in amino acids, alkaloids, vitamins, and xanthones; stems are rich in lignans; and leaves have the highest relative content of phenylpropanoids, ketoaldehydic acids, quinones, sugars and alcohols, terpenoids, coumarins, lipids, and others; meanwhile, the metabolite content is lower in roots. Among the dominant DEMs, 58 were in roots, including arachidonic acid, lucidone, isoliquiritigenin, etc.; 75 were in flowers, including mannose, shikimic acid, d-gluconic acid, kaempferol, etc.; 45 were in the fruit, including pterostilbene, l-ascorbic acid, riboflavin, etc.; 27 were in the stems, including salicylic acid, d-(-)-quinic acid, mannitol, (-)-catechin gallate, etc.; there was a maximum number of 119 dominant metabolites in the leaves, including oleanolic acid, l-glucose, d-arabitol, eugenol, etc. In sum, the rich chemical composition of C. luteoflora and the significant differences in the relative contents of metabolites in different organs will provide theoretical references for the study of tea, flower tea, edible oil, nutraceuticals, and the medicinal components of C. luteoflora.


Subject(s)
Camellia , Flowers , Fruit , Metabolomics , Plant Leaves , Plant Roots , Tandem Mass Spectrometry , Metabolomics/methods , Plant Leaves/metabolism , Plant Leaves/chemistry , Flowers/metabolism , Flowers/chemistry , Camellia/metabolism , Camellia/chemistry , Fruit/metabolism , Fruit/chemistry , Plant Roots/metabolism , Plant Roots/chemistry , Plant Stems/metabolism , Plant Stems/chemistry , Chromatography, Liquid , Metabolome , Flavonoids/metabolism , Flavonoids/analysis , Metabolic Networks and Pathways , Terpenes/metabolism , Terpenes/analysis
9.
Physiol Plant ; 176(5): e14552, 2024.
Article in English | MEDLINE | ID: mdl-39377134

ABSTRACT

The biosynthesis and accumulation of secondary metabolites play a vital role in determining the quality of medicinal plants, with carbohydrate metabolism often influencing secondary metabolism. To understand the potential regulatory mechanism, exogenous sugars (sucrose, glucose/fructose) were applied to the leaves of Cyclocarya paliurus, a highly valued and multiple function tree species. The results showed that exogenous sugars enhanced the accumulation of soluble sugar and starch while increasing the enzyme activity related to carbohydrate metabolism. In addition, the plant height was increased by a mixture of exogenous mixed sugars, the addition of sucrose promoted the net photosynthetic rate, while all types of exogenous sugars facilitated the accumulation of flavonoids and terpenoids. Based on weighted gene co-expression network analysis (WGCNA), two key gene modules and four candidate transcription factors (TFs) related to carbohydrate metabolism and secondary metabolite biosynthesis were identified. A correlation analysis between transcriptome and metabolome data showed that exogenous sugar up-regulated the expression of key structural genes in the flavonoid and terpenoid biosynthetic pathway. The expression levels of the four candidate TFs, TIFY 10A, WRKY 7, EIL 3 and RF2a, were induced by exogenous sugar and were strongly correlated with the key structural genes, which enhanced the synthesis of specific secondary metabolites and some plant hormone signal pathways. Our results provide a comprehensive understanding of key factors in the quality formation of medicinal plants and a potential approach to improve the quality.


Subject(s)
Gene Expression Regulation, Plant , Juglandaceae , Secondary Metabolism , Juglandaceae/metabolism , Juglandaceae/genetics , Gene Expression Regulation, Plant/drug effects , Secondary Metabolism/genetics , Flavonoids/metabolism , Flavonoids/biosynthesis , Plant Leaves/metabolism , Plant Leaves/genetics , Sugars/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Carbohydrate Metabolism , Terpenes/metabolism , Sucrose/metabolism , Transcriptome/genetics , Photosynthesis , Metabolome/drug effects , Starch/metabolism
10.
Physiol Plant ; 176(5): e14559, 2024.
Article in English | MEDLINE | ID: mdl-39377160

ABSTRACT

Litchi (Litchi chinensis Sonn.) has a desirable sweet taste and exotic aroma, making it popular in the markets. However, the biosynthesis of aroma volatiles in litchi fruit has rarely been investigated. In this study, the content and composition of volatile compounds were determined during litchi fruit ripening. In the mature green and mature red stages of litchi, 49 and 45 volatile compounds were detected, respectively. Monoterpenes were found to be the most abundant volatile compounds in mature red fruit, and their contents significantly increased compared to green fruit, mainly including citronellol, geraniol, myrcene, and D-limonene, which contributed to the aroma in litchi fruit. By comparing the expression profiles of the genes involved in the terpene synthesis pathway during fruit development, a terpene synthesis gene (LcTPS1-2) was identified and characterized as a major player in the synthesis of monoterpenes and sesquiterpenes. A subcellular localization analysis found LcTPS1-2 to be present in the plastid and cytoplasm. The recombinant LcTPS1-2 enzyme was able to catalyze the formation of three monoterpenes, myrcene, geraniol and citral, from geranyl pyrophosphate (GPP) and to convert farnesyl diphosphate (FPP) to a sesquiterpene, caryophyllene in vitro. Transgenic Arabidopsis thaliana plants overexpressing LcTPS1-2 exclusively released one monoterpene D-limonene, and three sesquiterpenes cis-thujopsene, (E)-ß-famesene and trans-ß-ionone. These results indicate that LcTPS1-2 plays an important role in the production of major volatile terpenes in litchi fruit and provides a basis for future investigations of terpenoid biosynthesis in litchi and other horticultural crops.


Subject(s)
Fruit , Litchi , Monoterpenes , Plant Proteins , Sesquiterpenes , Volatile Organic Compounds , Fruit/metabolism , Fruit/genetics , Fruit/growth & development , Litchi/genetics , Litchi/metabolism , Sesquiterpenes/metabolism , Monoterpenes/metabolism , Volatile Organic Compounds/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Terpenes/metabolism , Acyclic Monoterpenes/metabolism
11.
BMC Genomics ; 25(1): 936, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375591

ABSTRACT

Lichen-forming fungi (LFF) are prolific producers of functionally and structurally diverse secondary metabolites, most of which are taxonomically exclusive and play lineage-specific roles. To date, widely distributed, evolutionarily conserved biosynthetic pathways in LFF are not known. However, this idea stems from polyketide derivatives, since most biochemical research on lichens has concentrated on polyketide synthases (PKSs). Here, we present the first systematic identification and comparison of terpene biosynthetic genes of LFF using all the available Lecanoromycete reference genomes and 22 de novo sequenced ones (111 in total, representing 60 genera and 23 families). We implemented genome mining and gene networking approaches to identify and group the biosynthetic gene clusters (BGCs) into networks of similar BGCs. Our large-scale analysis led to the identification of 724 terpene BGCs with varying degrees of pairwise similarity. Most BGCs in the dataset were unique with no similarity to a previously known fungal or bacterial BGC or among each other. Remarkably, we found two BGCs that were widely distributed in LFF. Interestingly, both conserved BGCs contain the same core gene, i.e., putatively a squalene/phytoene synthase (SQS), involved in sterol biosynthesis. This indicates that early gene duplications, followed by gene losses/gains and gene rearrangement are the major evolutionary factors shaping the composition of these widely distributed SQS BGCs across LFF. We provide an in-depth overview of these BGCs, including the transmembrane, conserved, variable and LFF-specific regions. Our study revealed that lichenized fungi do have a highly conserved BGC, providing the first evidence that a biosynthetic gene may constitute essential genes in lichens.


Subject(s)
Farnesyl-Diphosphate Farnesyltransferase , Lichens , Multigene Family , Terpenes , Lichens/genetics , Lichens/enzymology , Terpenes/metabolism , Farnesyl-Diphosphate Farnesyltransferase/genetics , Farnesyl-Diphosphate Farnesyltransferase/metabolism , Biosynthetic Pathways/genetics , Phylogeny , Genome, Fungal
12.
Cells ; 13(18)2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39329714

ABSTRACT

Threonine phosphorylation promotes inflammatory functions of STAT1 while restricting its interferon (IFN) signaling in innate immune responses. However, it remains unclear whether the restriction of STAT1-mediated IFN signaling conferred by threonine phosphorylation is a ubiquitous mechanism or one that is context-dependent. To address this, we utilized pristane-induced lupus, a prototype IFN-driven systemic autoimmune disease model characterized by the production of high-titer autoantibodies against nucleic acid-associated antigens. Through genetic and biochemical assays, we demonstrate that Thr748 phosphorylation is dispensable for STAT1 functionality in pristane-induced lupus. Genetically engineered mice expressing the phospho-deficient threonine 748-to-alanine (T748A) mutant STAT1 exhibited similar survival rates, high titers of anti-dsDNA IgG, and nephritis compared to their wild-type littermates. In sharp contrast, STAT1 deficiency protected mice against pristane-induced lupus, as evidenced by increased survival, low titers of anti-dsDNA IgG, and less severe nephritis in the STAT1 knockout mice compared to their T748A littermates. Our study suggests a phosphorylation-dependent modularity that governs the spectrum of STAT1 functionality in inflammatory contexts: IFN phospho-tyrosine-dependent and inflammatory phospho-threonine-dependent, with Thr748 phosphorylation driving selective inflammatory activities, particularly those not driven by the canonical JAK pathway. From a broader perspective, our findings provide deeper insights into how distinct phosphorylation events shape the combinatorial logic of signaling cassettes, thereby regulating context-dependent responses.


Subject(s)
Inflammation , STAT1 Transcription Factor , Threonine , Animals , Phosphorylation , STAT1 Transcription Factor/metabolism , Threonine/metabolism , Mice , Inflammation/pathology , Inflammation/metabolism , Signal Transduction , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/pathology , Lupus Erythematosus, Systemic/immunology , Mice, Knockout , Mice, Inbred C57BL , Terpenes
13.
Mar Drugs ; 22(9)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39330273

ABSTRACT

A chemical investigation of the extracts from the soft coral Litophyton brassicum led to the isolation and identification of four new meroterpenes, brassihydroxybenzoquinone A and B (1 and 2) and brassinaphthoquinone A and B (3 and 4), along with two known related meroterpenes (5 and 6). Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR) spectroscopy, and a comparison with the literature data. All compounds were evaluated for antibacterial activity against six pathogenic bacterial strains and for cytotoxic activity against three cancer cell lines. In the cytotoxic assay, all compounds were inactive at 10 µM against the A549, HeLa, and MDA-MB-231 cell lines. In the antibacterial assay, compounds 1 and 2 exhibited moderate inhibitory activity with minimum inhibitory concentrations (MIC) ranging from 8 to 64 µg/mL.


Subject(s)
Anthozoa , Anti-Bacterial Agents , Microbial Sensitivity Tests , Terpenes , Anthozoa/chemistry , Animals , Humans , Cell Line, Tumor , Terpenes/pharmacology , Terpenes/chemistry , Terpenes/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , China , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Magnetic Resonance Spectroscopy , HeLa Cells , Spectrometry, Mass, Electrospray Ionization , Molecular Structure
14.
Mar Drugs ; 22(9)2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39330306

ABSTRACT

Meroterpenoid-type marine natural compounds have attracted an increasing amount of attention due to their peculiar chemical structures and their potential for the development of therapeutically important probes. Within this group of substances pelorol stands out; it is a natural compound isolated from marine organisms with a unique structure and an interesting biological profile. In this article, we summarize and highlight the most interesting aspects of the synthetic procedures towards this compound, which have two common key steps. The first is the coupling of a drimanyl derivative with a compound derived from an arene. The second is a Friedel-Crafts cyclization which forms the C ring of the natural product. Despite the synthetic advances achieved so far, we consider that a more efficient synthetic procedures could be carried out, since their synthetic routes are difficult to scale up due to numerous reaction steps and the limitations imposed by the use of some reagents. In this article, we present a new and versatile retrosynthetic analysis of (-)-pelorol and analogs, which is highly desirable for their easy preparation and subsequent broad study of their biological activities. This is a retrosynthetic route that could improve those reported in the literature in terms of cost-effectiveness.


Subject(s)
Aquatic Organisms , Biological Products , Biological Products/chemical synthesis , Biological Products/chemistry , Cyclization , Animals , Terpenes/chemical synthesis , Terpenes/chemistry , Sesquiterpenes/chemical synthesis , Sesquiterpenes/chemistry , Molecular Structure
15.
Pak J Pharm Sci ; 37(3): 583-590, 2024 May.
Article in English | MEDLINE | ID: mdl-39340849

ABSTRACT

Gardenia jasminoides suspension culture has gained recognition as a functional approach for bioactive component development in the pharmaceutical industries but exhibits limited biomass accumulation and secondary metabolite production. This study presents the first record of maximum biomass production and demonstrates the cumulative levels of phenols, flavonoids and terpenoids observed through the growth trajectory of G. jasminoides suspension culture. Successful callus induction was obtained from leaf explants cultured on Murashige and Skoog (MS) medium augmented with a standardized conjunction of 1 mg/L of 2,4-Dichlorophenoxyacetic acid (2,4-D) and 0.5 mg/L kinetin (KT). The experimental outcomes revealed that on the 35th day, the in vitro suspension culture exhibited the highest biomass accumulation which was 5.43 times greater than the initial inoculation level. The study quantified total phenols, flavonoids, and terpenoids present in leaf explants, callus cultures, and suspension cultures and determined antioxidant efficacy. Findings suggest that an optimized growth regulator in G. jasminoides suspension culture significantly increases biomass accumulation. Quantification of secondary metabolites offers a promising path for future enhancement of their yield through elicitation and holds the potential to achieve extensive yield of cost-effective bioactive components.


Subject(s)
Antioxidants , Biomass , Flavonoids , Gardenia , Phenols , Antioxidants/metabolism , Antioxidants/pharmacology , Flavonoids/metabolism , Flavonoids/analysis , Phenols/metabolism , Gardenia/chemistry , Gardenia/metabolism , Gardenia/growth & development , Plant Leaves/metabolism , Plant Leaves/growth & development , Terpenes/metabolism , Secondary Metabolism , Plant Extracts/pharmacology , Plant Growth Regulators/pharmacology
16.
Nat Commun ; 15(1): 8307, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39333063

ABSTRACT

In pharmaceutical discovery, the "magic methyl" effect describes a substantial improvement in the pharmacological properties of a drug candidate with the incorporation of methyl groups. Therefore, to expedite the synthesis of methylated drug analogs, late-stage, undirected methylations of C(sp3)-H bonds in complex molecules would be valuable. However, current methods for site-selective methylations are limited to activated C(sp3)-H bonds. Here we describe a site-selective, undirected methylation of unactivated C(sp3)-H bonds, enabled by photochemically activated peroxides and a nickel(II) complex whose turnover is enhanced by an ancillary ligand. The methodology displays compatibility with a wide range of functional groups and a high selectivity for tertiary C-H bonds, making it suitable for the late-stage methylation of complex organic compounds that contain multiple alkyl C-H bonds, such as terpene natural products, peptides, and active pharmaceutical ingredients. Overall, this method provides a synthetic tool to explore the "magic methyl" effect in drug discovery.


Subject(s)
Nickel , Methylation , Catalysis , Nickel/chemistry , Peroxides/chemistry , Drug Discovery/methods , Biological Products/chemistry , Ligands , Terpenes/chemistry , Terpenes/metabolism , Peptides/chemistry , Carbon/chemistry
17.
BMC Plant Biol ; 24(1): 915, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39350013

ABSTRACT

BACKGROUND: Amomum tsao-ko is an important aromatic crop used in medicines and food. It can be categorized into three main types based on the fruit shape: long (L), oval (O), and round (R). However, limited information is available on the volatile substances present in differently shaped A. tsao-ko fruits. This study investigated the characteristics and biosynthesis of volatile organic compounds (VOCs) in fresh and dried A. tsao-ko fruits of different shapes using widely targeted volatilomics and transcriptome analyses. RESULTS: In total, 978 VOCs, primarily terpenoids, esters, and heterocyclic compounds, were detected. The number of differentially accumulated volatile organic compounds (DAVOCs) in dried fruits of various shapes was significantly higher than that in fresh fruits, with terpenoids, esters, and heterocyclic compounds accounting for approximately 50% of the total DAVOCs. Notably, α-phellandrene, identified as a shared differential accumulated terpenoid across various fruit shapes, was detected in both fresh and dried fruits. Through transcriptome analysis, 40 candidate genes implicated in the terpenoid biosynthesis pathway were screened. An integrated analysis of the metabolome and transcriptome revealed that the structural genes HMGR-2, TPS7, TPS5-10, TPS21-3, TPS21-5, TPS21-6, TPS21-7, and TPS21-9, along with 81 transcription factors (including 17 NACs, 16 MYBs, 16 AP2/ERFs, 13 WRKYs, 13 bHLHs, and 6 bZIPs), co-regulate the biosynthesis of volatile terpenoids. CONCLUSIONS: This study expands our understanding of the volatile metabolism profile of A. tsao-ko and provides a solid foundation for future investigations of the mechanisms governing fruit quality.


Subject(s)
Amomum , Fruit , Gene Expression Profiling , Terpenes , Volatile Organic Compounds , Volatile Organic Compounds/metabolism , Fruit/genetics , Fruit/metabolism , Fruit/chemistry , Amomum/genetics , Amomum/metabolism , Amomum/chemistry , Terpenes/metabolism , Transcriptome , Gene Expression Regulation, Plant
18.
Parasitol Res ; 123(9): 315, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39227462

ABSTRACT

Mosquito-borne diseases, such as malaria, dengue fever, and the Zika virus, pose significant global health challenges, affecting millions annually. Due to increasing insecticide resistance, there is a growing interest in natural alternatives for mosquito control. Lemongrass essential oil, derived from Cymbopogon citratus, has shown promising repellent and larvicidal properties against various mosquito species. In this study, we investigated the larvicidal effect of lemongrass oil and its major compounds on Anopheles sinensis, the primary malaria vector in China. GC-MS analysis identified the major compounds of lemongrass oil as ( +)-citronellal (35.60%), geraniol (21.84%), and citronellol (13.88%). Lemongrass oil showed larvicidal activity against An. sinensis larvae, with an LC50 value of 119.20 ± 3.81 mg/L. Among the major components, citronellol had the lowest LC50 value of 42.76 ± 3.18 mg/L. Moreover, citronellol demonstrated inhibitory effects on acetylcholinesterase (AChE) activity in An. sinensis larvae, assessed by homogenizing larvae at different time points following treatment. Molecular docking studies further elucidated the interaction between citronellol and AChE, revealing the formation of hydrogen bonds and Pi-Sigma bonds. Aromatic amino acid residues such as Tyr71, Trp83, Tyr370, and Tyr374 played a pivotal role in these interactions. These findings may contribute to understanding lemongrass oil's larvicidal activity against An. sinensis and the mechanisms underlying these effects.


Subject(s)
Acyclic Monoterpenes , Anopheles , Cholinesterase Inhibitors , Insecticides , Larva , Oils, Volatile , Plant Oils , Animals , Anopheles/drug effects , Anopheles/enzymology , Larva/drug effects , Insecticides/pharmacology , Insecticides/chemistry , Acyclic Monoterpenes/pharmacology , Plant Oils/pharmacology , Plant Oils/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Cymbopogon/chemistry , Molecular Docking Simulation , Terpenes/pharmacology , Terpenes/chemistry , Gas Chromatography-Mass Spectrometry , China , Acetylcholinesterase/metabolism , Mosquito Vectors/drug effects , Monoterpenes/pharmacology , Monoterpenes/chemistry , Aldehydes/pharmacology , Aldehydes/chemistry
19.
Int J Mol Sci ; 25(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39337440

ABSTRACT

Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, ß-sitosterol and 3ß-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, ß-phenylethanol, dodecane, ß-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential.


Subject(s)
Anti-Inflammatory Agents , Antioxidants , Carbon Dioxide , Flowers , Plant Extracts , Rhododendron , Rhododendron/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Flowers/chemistry , Carbon Dioxide/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Terpenes/chemistry , Terpenes/pharmacology , Chromatography, Supercritical Fluid/methods , Tandem Mass Spectrometry
20.
Ann Agric Environ Med ; 31(3): 340-344, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39344721

ABSTRACT

INTRODUCTION AND OBJECTIVE: Medicinal plants have a long and significant history of being used for their healing properties. One famous example is Commiphora, which is mostly found in the southern part of Arabia. The objective of this study was to evaluate the effectiveness of a water-based extract obtained from two different varieties of myrrh in suppressing the proliferation of Candida spp. at different concentrations. MATERIAL AND METHODS: The inhibitory activity of the aqueous extract of two different varieties of myrrh, commonly used in traditional medicine, was assessed against five pathogenic yeasts using the diffusion technique. Mass spectrum was used to analyze myrrh's chemical composition for antimicrobial effects. RESULTS: The aqueous extract of both tested species of myrrh (Commiphora myrrha and Commiphora molmol) showed inhibitory effects on all tested isolates. During the chemical examination of myrrh, it was noted that the material included 12 components known for their antimicrobial properties. The essential oil derived from two varieties of myrrh showed the most significant effects on Candida tropicalis (ATCC 66029), Candida guilliermondii (ATCC 6260), Candida laurentii (ATCC 18803), Candida neoformans (ATCC 66031), and Candida albicans (ATCC 14053). Analysis of chemical composition of the myrrh revealed 19 known components, of which 12 compounds have been proven by research to suppress the growth of microorganisms. CONCLUSIONS: C. myrrha and C. molmol aqueous extracts exhibit a promising antifungal effect against common Candida infections. The aqueous extracts present a variety of antimicrobial compounds; however, further research is necessary to elucidate the specific mechanisms of action of these compounds, and to evaluate their efficacy, toxicity and safety before considering their clinical application.


Subject(s)
Antifungal Agents , Candida , Commiphora , Resins, Plant , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Commiphora/chemistry , Candida/drug effects , Resins, Plant/chemistry , Resins, Plant/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Microbial Sensitivity Tests , Terpenes/pharmacology , Terpenes/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry
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