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1.
Int J Mol Sci ; 22(24)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34948297

RESUMO

Six strawberry genotypes were examined for fruit yield and size, important chemical traits (sugars, phenolics, anthocyanins, ascorbic acid, volatiles) and antioxidant properties (ferric reducing power). In addition, we determined the expression of genes and transcription factors (SAAT, FaNES1, FaFAD1, FaEGS2, FaEOBII and FaMYB10) controlling the main flavor and aroma traits, and finally evaluated the effect of the genotype and harvest time on the examined chemical and genetic factors, as well as their intercorrelations. The commercial varieties 'Fortuna', 'Victory', 'Calderon', 'Rociera', and two advanced selections Ber22/6 and Ber23/3 were cultivated under the same conditions at Berryplasma World Ltd. plantations (Varda, Ilia, Region of Western Greece). Strawberries were harvested at three different time points over the main harvest period in Greece, i.e., early March (T1), late March (T2) and late April (T3). 'Fortuna' exhibited the highest early and total yield, while 'Calderon', the highest average berry weight. General Linear Model repeated measures ANOVA demonstrated that the interaction of the genotype and harvest time was significant (p < 0.001) on all tested quality attributes and gene expression levels, showing that each genotype behaves differently throughout the harvest period. Exceptions were observed for: (a) the volatile anhydrides, fatty acids, aromatics and phenylpropanoids (all were greatly affected by the harvest time), and (b) lactones, furaneol and FaEGS2 that were affected only by the genotype. We observed significant intercorrelations among those factors, e.g., the positive correlation of FaFAD1 expression with decalactone and nerolidol, of SAAT with furaneol, trans-cinnamic acid and phenylpropanoids, and of FaEGS2 with decalactone and FaFAD1. Moreover, a strong positive correlation between SAAT and FaMYB10 and a moderate negative one between SAAT and glucose were also detected. Those correlations can be further investigated to reveal potential markers for strawberry breeding. Overall, our study contributes to a better understanding of strawberry physiology, which would facilitate breeding efforts for the development of new strawberry varieties with superior qualitative traits.


Assuntos
Aromatizantes/metabolismo , Fragaria/genética , Locos de Características Quantitativas/genética , Compostos Orgânicos Voláteis/metabolismo , Antioxidantes/metabolismo , Fragaria/metabolismo , Frutas/genética , Frutas/metabolismo , Genótipo , Glucose/genética , Glucose/metabolismo , Grécia , Odorantes , Sesquiterpenos/metabolismo , Paladar/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Biochemistry ; 60(51): 3868-3878, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34898176

RESUMO

Valerena-1,10-diene synthase (VDS) catalyzes the conversion of the universal precursor farnesyl diphosphate into the unusual sesquiterpene valerena-1,10-diene (VLD), which possesses a unique isobutenyl substituent group. In planta, one of VLD's isobutenyl terminal methyl groups becomes oxidized to a carboxylic acid forming valerenic acid (VA), an allosteric modulator of the GABAA receptor. Because a structure-activity relationship study of VA for its modulatory activity is desired, we sought to manipulate the VDS enzyme for the biosynthesis of structurally diverse scaffolds that could ultimately lead to the generation of VA analogues. Using three-dimensional structural homology models, phylogenetic sequence comparisons to well-characterized sesquiterpene synthases, and a substrate-active site contact mapping approach, the contributions of specific amino acid residues within or near the VDS active site to possible catalytic cascades for VLD and other sesquiterpene products were assessed. An essential role of Tyr535 in a germacrenyl route to VLD was demonstrated, while its contribution to a family of other sesquiterpenes derived from a humulyl route was not. No role for Cys415 or Cys452 serving as a proton donor to reaction intermediates in VLD biosynthesis was observed. However, a gatekeeper role for Asn455 in directing farnesyl carbocations down all-trans catalytic cascades (humulyl and germacrenyl routes) versus a cisoid cascade (nerolidyl route) was demonstrated. Altogether, these results have mapped residues that establish a context for the catalytic cascades operating in VDS and future manipulations for generating more structurally constrained scaffolds.


Assuntos
Alquil e Aril Transferases/química , Alquil e Aril Transferases/metabolismo , Sesquiterpenos/metabolismo , Alquil e Aril Transferases/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Biocatálise , Domínio Catalítico/genética , Cinética , Redes e Vias Metabólicas , Modelos Moleculares , Mutagênese Sítio-Dirigida , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrutura Terciária de Proteína , Sesquiterpenos/química , Especificidade por Substrato , Valeriana/enzimologia , Valeriana/genética
3.
Elife ; 102021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632981

RESUMO

Gut enzymes can metabolize plant defense compounds and thereby affect the growth and fitness of insect herbivores. Whether these enzymes also influence feeding preference is largely unknown. We studied the metabolization of taraxinic acid ß-D-glucopyranosyl ester (TA-G), a sesquiterpene lactone of the common dandelion (Taraxacum officinale) that deters its major root herbivore, the common cockchafer larva (Melolontha melolontha). We have demonstrated that TA-G is rapidly deglucosylated and conjugated to glutathione in the insect gut. A broad-spectrum M. melolontha ß-glucosidase, Mm_bGlc17, is sufficient and necessary for TA-G deglucosylation. Using cross-species RNA interference, we have shown that Mm_bGlc17 reduces TA-G toxicity. Furthermore, Mm_bGlc17 is required for the preference of M. melolontha larvae for TA-G-deficient plants. Thus, herbivore metabolism modulates both the toxicity and deterrence of a plant defense compound. Our work illustrates the multifaceted roles of insect digestive enzymes as mediators of plant-herbivore interactions.


Assuntos
Besouros/enzimologia , Glucosídeos/metabolismo , Herbivoria , Proteínas de Insetos/metabolismo , Lactonas/metabolismo , Sesquiterpenos/metabolismo , Taraxacum/metabolismo , beta-Galactosidase/metabolismo , Animais , Besouros/embriologia , Besouros/genética , Digestão , Glucosídeos/toxicidade , Glutationa/metabolismo , Hidrólise , Inativação Metabólica , Proteínas de Insetos/genética , Lactonas/toxicidade , Larva/enzimologia , Larva/genética , Metabolismo Secundário , Sesquiterpenos/toxicidade , Taraxacum/toxicidade , beta-Galactosidase/genética
4.
Arch Biochem Biophys ; 711: 109028, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34509463

RESUMO

Elevated expression of thioredoxin reductase (TrxR) is associated with the tumorigenesis and resistance to cancer chemoradiotherapy, highlighting the potential of TrxR inhibitors as anticancer drugs. Deoxyelephantopin (DET) is the major active ingredient of Elephantopus scaber and reveals potent anticancer activity. However, the potential mechanism of action and the cellular target of DET are still unknown. Here, we found that DET primarily targets the Sec residue of TrxR and irreversibly prohibits enzyme activity. Suppression of TrxR by DET leads to accumulation of reactive oxygen species and dysregulation in intracellular redox balance, eventually inducing cancer cell apoptosis mediated by oxidative stress. Noticeably, down-regulation of TrxR1 by shRNA increases cell sensitivity to DET. Collectively, targeting of TrxR1 by DET uncovers a novel mechanism of action in DET and deepens the understanding of developing DET as a potential chemotherapeutic agent for treating cancers.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Células HeLa , Humanos , Lactonas/metabolismo , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo
5.
Int J Mol Sci ; 22(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34576244

RESUMO

Drought stress causes heavy damages to crop growth and productivity under global climatic changes. Transcription factors have been extensively studied in many crops to play important roles in plant growth and defense. However, there is a scarcity of studies regarding WRKY transcription factors regulating drought responses in maize crops. Previously, ZmWRKY79 was identified as the regulator of maize phytoalexin biosynthesis with inducible expression under different elicitation. Here, we elucidated the function of ZmWRKY79 in drought stress through regulating ABA biosynthesis. The overexpression of ZmWRKY79 in Arabidopsis improved the survival rate under drought stress, which was accompanied by more lateral roots, lower stomatal aperture, and water loss. ROS scavenging was also boosted by ZmWRKY79 to result in less H2O2 and MDA accumulation and increased antioxidant enzyme activities. Further analysis detected more ABA production in ZmWRKY79 overexpression lines under drought stress, which was consistent with up-regulated ABA biosynthetic gene expression by RNA-seq analysis. ZmWRKY79 was observed to target ZmAAO3 genes in maize protoplast through acting on the specific W-boxes of the corresponding gene promoters. Virus-induced gene silencing of ZmWRKY79 in maize resulted in compromised drought tolerance with more H2O2 accumulation and weaker root system architecture. Together, this study substantiates the role of ZmWRKY79 in the drought-tolerance mechanism through regulating ABA biosynthesis, suggesting its broad functions not only as the regulator in phytoalexin biosynthesis against pathogen infection but also playing the positive role in abiotic stress response, which provides a WRKY candidate gene to improve drought tolerance for maize and other crop plants.


Assuntos
Ácido Abscísico/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo , Zea mays/metabolismo , Antioxidantes/metabolismo , Arabidopsis , Inativação Gênica , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas , Estômatos de Plantas , Plantas Geneticamente Modificadas/metabolismo , Regiões Promotoras Genéticas , RNA-Seq , Sesquiterpenos/metabolismo , Estresse Fisiológico/genética , Transcriptoma
6.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500778

RESUMO

Parthenin, a sesquiterpene lactone of pseudoguaianolide type, is the representative secondary metabolite of the tropical weed Parthenium hysterophorus (Asteraceae). It accounts for a multitude of biological activities, including toxicity, allergenicity, allelopathy, and pharmacological aspects of the plant. Thus far, parthenin and its derivatives have been tested for chemotherapeutic abilities, medicinal properties, and herbicidal/pesticidal activities. However, due to the lack of toxicity-bioactivity relationship studies, the versatile properties of parthenin are relatively less utilised. The possibility of exploiting parthenin in different scientific fields (e.g., chemistry, medicine, and agriculture) makes it a subject of analytical discussion. The present review highlights the multifaceted uses of parthenin, on-going research, constraints in the practical applicability, and the possible workarounds for its successful utilisation. The main aim of this comprehensive discussion is to bring parthenin to the attention of researchers, pharmacologists, natural product chemists, and chemical biologists and to open the door for its multidimensional applications.


Assuntos
Asteraceae/química , Sesquiterpenos/farmacologia , Asteraceae/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-34339956

RESUMO

Ylang-ylang (YY) essential oil (EO) is distilled from the fresh-mature flowers of the Annonaceae family tropical tree Cananga odorata [Lam.] Hook. f. & Thomson, and is widely used in perfume and cosmetic industries for its fragrant character. Herein, two different metabolomic profiles obtained using high-performance thin-layer chromatography (HPTLC), applying different stains, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH·) and p-anisaldehyde, were used for discrimination of 52 YY samples across geographical origins and distillation grades. The first profile is developed using the DPPH· stain based on the radical scavenging activity (RSA) of YY EOs. Results of the HPTLC-DPPH· assay confirmed that RSA of YY EOs is in proportion to the length of distillation times. Major components contributing to the RSA of YY EOs were tentatively identified as germacrene D and α-farnesene, eugenol and linalool, by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionisation detector (GC-FID). The second profile was developed using the general-purpose p-anisaldehyde stain based on the general chemical composition of YY EOs. Untargeted metabolomic discrimination of YY EOs from different geographical origins was performed based on the HPTLC-p-anisaldehyde profiles, followed by principal component analysis (PCA). A discrimination and prediction model for identification of YY distillation grade was developed using PCA and partial least squares regression (PLS) based on binned HPTLC-ultraviolet (254 nm) profiles, which was successfully applied to distillation grade determination of blended YY Complete EOs.


Assuntos
Cananga/química , Cromatografia em Camada Delgada/métodos , Sequestradores de Radicais Livres/química , Óleos Voláteis/química , Óleos Vegetais/química , Compostos de Bifenilo/análise , Compostos de Bifenilo/metabolismo , Cromatografia Líquida de Alta Pressão , Destilação , Eugenol/análise , Eugenol/química , Eugenol/metabolismo , Sequestradores de Radicais Livres/metabolismo , Metabolômica , Análise Multivariada , Óleos Voláteis/metabolismo , Picratos/análise , Picratos/metabolismo , Óleos Vegetais/metabolismo , Sesquiterpenos/análise , Sesquiterpenos/química , Sesquiterpenos/metabolismo
8.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361731

RESUMO

Strigolactones (SLs) are a class of sesquiterpenoid plant hormones that play a role in the response of plants to various biotic and abiotic stresses. When released into the rhizosphere, they are perceived by both beneficial symbiotic mycorrhizal fungi and parasitic plants. Due to their multiple roles, SLs are potentially interesting agricultural targets. Indeed, the use of SLs as agrochemicals can favor sustainable agriculture via multiple mechanisms, including shaping root architecture, promoting ideal branching, stimulating nutrient assimilation, controlling parasitic weeds, mitigating drought and enhancing mycorrhization. Moreover, over the last few years, a number of studies have shed light onto the effects exerted by SLs on human cells and on their possible applications in medicine. For example, SLs have been demonstrated to play a key role in the control of pathways related to apoptosis and inflammation. The elucidation of the molecular mechanisms behind their action has inspired further investigations into their effects on human cells and their possible uses as anti-cancer and antimicrobial agents.


Assuntos
Antineoplásicos/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Lactonas/farmacologia , Micorrizas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Plantas/metabolismo , Sesquiterpenos/farmacologia , Adaptação Fisiológica , Agricultura/métodos , Agroquímicos/isolamento & purificação , Agroquímicos/metabolismo , Agroquímicos/farmacologia , Antibacterianos/biossíntese , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/metabolismo , Humanos , Inflamação/prevenção & controle , Lactonas/isolamento & purificação , Lactonas/metabolismo , Micorrizas/química , Neoplasias/tratamento farmacológico , Patentes como Assunto , Reguladores de Crescimento de Plantas/biossíntese , Reguladores de Crescimento de Plantas/isolamento & purificação , Plantas/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/metabolismo , Estresse Fisiológico , Controle de Plantas Daninhas/métodos
9.
Sci Rep ; 11(1): 17094, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429465

RESUMO

Linalool and nerolidol are terpene alcohols that occur naturally in many aromatic plants and are commonly used in food and cosmetic industries as flavors and fragrances. In plants, linalool and nerolidol are biosynthesized as a result of respective linalool synthase and nerolidol synthase, or a single linalool/nerolidol synthase. In our previous work, we have isolated a linalool/nerolidol synthase (designated as PamTps1) from a local herbal plant, Plectranthus amboinicus, and successfully demonstrated the production of linalool and nerolidol in an Escherichia coli system. In this work, the biochemical properties of PamTps1 were analyzed, and its 3D homology model with the docking positions of its substrates, geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15) in the active site were constructed. PamTps1 exhibited the highest enzymatic activity at an optimal pH and temperature of 6.5 and 30 °C, respectively, and in the presence of 20 mM magnesium as a cofactor. The Michaelis-Menten constant (Km) and catalytic efficiency (kcat/Km) values of 16.72 ± 1.32 µM and 9.57 × 10-3 µM-1 s-1, respectively, showed that PamTps1 had a higher binding affinity and specificity for GPP instead of FPP as expected for a monoterpene synthase. The PamTps1 exhibits feature of a class I terpene synthase fold that made up of α-helices architecture with N-terminal domain and catalytic C-terminal domain. Nine aromatic residues (W268, Y272, Y299, F371, Y378, Y379, F447, Y517 and Y523) outlined the hydrophobic walls of the active site cavity, whilst residues from the RRx8W motif, RxR motif, H-α1 and J-K loops formed the active site lid that shielded the highly reactive carbocationic intermediates from the solvents. The dual substrates use by PamTps1 was hypothesized to be possible due to the architecture and residues lining the catalytic site that can accommodate larger substrate (FPP) as demonstrated by the protein modelling and docking analysis. This model serves as a first glimpse into the structural insights of the PamTps1 catalytic active site as a multi-substrate linalool/nerolidol synthase.


Assuntos
Monoterpenos Acíclicos/metabolismo , Alquil e Aril Transferases/metabolismo , Proteínas de Plantas/metabolismo , Plectranthus/enzimologia , Sesquiterpenos/metabolismo , Alquil e Aril Transferases/química , Domínio Catalítico , Escherichia coli , Simulação de Acoplamento Molecular , Proteínas de Plantas/química , Fosfatos de Poli-Isoprenil/metabolismo , Ligação Proteica , Especificidade por Substrato
10.
Eur J Med Chem ; 224: 113675, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34229108

RESUMO

Melampomagnolide B (MMB, 3) is a parthenolide (PTL, 1) based sesquiterpene lactone that has been used as a template for the synthesis of a plethora of lead anticancer agents owing to its reactive C-10 primary hydroxyl group. Such compounds have been shown to inhibit the IKKß subunit, preventing phosphorylation of the cytoplasmic IκB inhibitory complex. The present study focuses on the synthesis and in vitro antitumor properties of novel benzyl and phenethyl carbamates of MMB (7a-7k). Screening of these MMB carbamates identified analogs with potent growth inhibition properties against a panel of 60 human cancer cell lines (71% of the molecules screened had GI50 values < 2 µM). Two analogs, the benzyl carbamate 7b and the phenethyl carbamate7k, were the most active compounds. Lead compound 7b inhibited cell proliferation in M9 ENL AML cells, and in TMD-231, OV-MD-231 and SUM149 breast cancer cell lines. Interestingly, mechanistic studies showed that 7b did not inhibit p65 phosphorylation in M9 ENL AML and OV-MD-231 cells, but did inhibit phophorylation of both p65 and IκBα in SUM149 cells. 7b also reduced NFκB binding to DNA in both OV-MD-231 and SUM149 cells. Molecular docking studies indicated that 7b and 7k are both predicted to interact with the ubiquitin-like domain (ULD) of the IKKß subunit. These data suggest that in SUM149 cells, 7b is likely acting as an allosteric inhibitor of IKKß, whereas in M9 ENL AML and OV-MD-231 cells 7b is able to inhibit an event after IκB/p65/p50 phosphorylation by IKKß that leads to inhibition of NFκB activation and reduction in NFκB-DNA binding. Analog 7b was by far the most potent compound in either carbamate series, and was considered an important lead compound for further optimization and development as an anticancer agent.


Assuntos
Antineoplásicos/química , NF-kappa B/antagonistas & inibidores , Sesquiterpenos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Simulação de Acoplamento Molecular , NF-kappa B/química , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Domínios Proteicos , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade , Termodinâmica , Fator de Transcrição RelA/metabolismo
11.
BMC Plant Biol ; 21(1): 354, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315414

RESUMO

BACKGROUND: Atractylodes chinensis (DC.) Koidz is a well-known medicinal plant containing the major bioactive compound, atractylodin, a sesquiterpenoid. High-performance liquid chromatography (HPLC) analysis demonstrated that atractylodin was most abundant in 3-year old A. chinensis rhizome, compared with those from 1- and 2-year old rhizomes, however, the molecular mechanisms underlying accumulation of atractylodin in rhizomes are poorly understood. RESULTS: In this study, we characterized the transcriptomes from rhizomes of 1-, 2- and 3-year old (Y1, Y2 and Y3, respectively) A. chinensis, to identify differentially expressed genes (DEGs). We identified 240, 169 and 131 unigenes encoding the enzyme genes in the mevalonate (MVA), methylerythritol phosphate (MEP), sesquiterpenoid and triterpenoid biosynthetic pathways, respectively. To confirm the reliability of the RNA sequencing analysis, eleven key gene encoding factors involved in the sesquiterpenoid and triterpenoid biosynthetic pathway, as well as in pigment, amino acid, hormone and transcription factor functions, were selected for quantitative real time PCR (qRT-PCR) analysis. The results demonstrated similar expression patterns to those determined by RNA sequencing, with a Pearson's correlation coefficient of 0.9 between qRT-PCR and RNA-seq data. Differential gene expression analysis of rhizomes from different ages revealed 52 genes related to sesquiterpenoid and triterpenoid biosynthesis. Among these, seven DEGs were identified in Y1 vs Y2, Y1 vs Y3 and Y2 vs Y3, of which five encoded four key enzymes, squalene/phytoene synthase (SS), squalene-hopene cyclase (SHC), squalene epoxidase (SE) and dammarenediol II synthase (DS). These four enzymes directly related to squalene biosynthesis and subsequent catalytic action. To validate the result of these seven DEGs, qRT-PCR was performed and indicated most of them displayed lower relative expression in 3-year old rhizome, similar to transcriptomic analysis. CONCLUSION: The enzymes SS, SHC, SE and DS down-regulated expression in 3-year old rhizome. This data corresponded to the higher content of sesquiterpenoid in 3-year old rhizome, and confirmed by qRT-PCR. The results of comparative transcriptome analysis and identified key enzyme genes laid a solid foundation for investigation of production sesquiterpenoid in A. chinensis.


Assuntos
Atractylodes/metabolismo , Perfilação da Expressão Gênica/métodos , Transcriptoma/genética , Alquil e Aril Transferases/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Geranil-Geranildifosfato Geranil-Geraniltransferase/metabolismo , Transferases Intramoleculares/metabolismo , Análise de Sequência de RNA/métodos , Sesquiterpenos/metabolismo , Esqualeno Mono-Oxigenase/metabolismo
12.
Chem Biodivers ; 18(9): e2100397, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34302322

RESUMO

The red alga Laurencia nipponica comprises various chemical races distributed relative to the ocean current in Japanese coastal areas. We investigated the chemical compositions and chemical races of L. nipponica distributed from the Kunashiri and Etorofu Islands, the confluence of the Soya warm current and Oya-shio cold current. Two new halogenated secondary metabolites, deacetylneonipponallene (1) and neopacifenol (2), along with four known compounds, deoxyprepacifenol (3), pacifenol (4), halo-chamigrene diether (5), and isolaurallene (6) were isolated from L. nipponica collected at Chikappunai, Kunashiri Island, while Zaimokuiwa (Kunashiri Island) and Sana (Etorofu Island) populations contained 3, 7-hydroxylaurene (7), 2,10-dibromo-3-chloro-9-hydroxy-α-chamigrene (8), and (3Z)-laurefucin (9). The structures of 1 and 2 were established using spectroscopic methods. The chemical races of L. nipponica distributed in this area were divided into 6- and 9-producing races. Interestingly, both races contained 4 as an additional race-index, as well as its derivatives, 2 and 5. To the best of our knowledge, this is the first example of a race comprising a mixture of two race-index compounds, suggesting that the convergence of two currents causes the production of new and diverse chemical races in this species.


Assuntos
Laurencia/química , Sesquiterpenos/química , Halogenação , Ilhas , Japão , Conformação Molecular , Sesquiterpenos/metabolismo
13.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198531

RESUMO

Sesquiterpenes are important defense and signal molecules for plants to adapt to the environment, cope with stress, and communicate with the outside world, and their evolutionary history is closely related to physiological functions. In this study, the information of plant sesquiterpene synthases (STSs) with identified functions were collected and sorted to form a dataset containing about 500 members. The phylogeny of spermatophyte functional STSs was constructed based on the structural comparative analysis to reveal the sequence-structure-function relationships. We propose the evolutionary history of plant sesquiterpene skeletons, from chain structure to small rings, followed by large rings for the first time and put forward a more detailed function-driven hypothesis. Then, the evolutionary origins and history of spermatophyte STSs are also discussed. In addition, three newly identified STSs CaSTS2, CaSTS3, and CaSTS4 were analyzed in this functional evolutionary system, and their germacrene D products were consistent with the functional prediction. This demonstrates an application of the structure-based phylogeny in predicting STS function. This work will help us to understand evolutionary patterns and dynamics of plant sesquiterpenes and STSs and screen or design STSs with specific product profiles as functional elements for synthetic biology application.


Assuntos
Alquil e Aril Transferases/genética , Evolução Molecular , Plantas/enzimologia , Sesquiterpenos/metabolismo , Alquil e Aril Transferases/química , Sequência de Aminoácidos , Filogenia , Sesquiterpenos/química
14.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201662

RESUMO

Gene expression and phytohormone contents were measured in response to elevating ascorbate in the absence of other confounding stimuli such as high light and abiotic stresses. Young Arabidopsis plants were treated with 25 mM solutions of l-galactose pathway intermediates l-galactose (l-gal) or l-galactono-1,4-lactone (l-galL), as well as L-ascorbic acid (AsA), with 25 mM glucose used as control. Feeding increased rosette AsA 2- to 4-fold but there was little change in AsA biosynthetic gene transcripts. Of the ascorbate recycling genes, only Dehydroascorbate reductase 1 expression was increased. Some known regulatory genes displayed increased expression and included ANAC019, ANAC072, ATHB12, ZAT10 and ZAT12. Investigation of the ANAC019/ANAC072/ATHB12 gene regulatory network revealed a high proportion of ABA regulated genes. Measurement of a subset of jasmonate, ABA, auxin (IAA) and salicylic acid compounds revealed consistent increases in ABA (up to 4.2-fold) and phaseic acid (PA; up to 5-fold), and less consistently certain jasmonates, IAA, but no change in salicylic acid levels. Increased ABA is likely due to increased transcripts for the ABA biosynthetic gene NCED3. There were also smaller increases in transcripts for transcription factors ATHB7, ERD1, and ABF3. These results provide insights into how increasing AsA content can mediate increased abiotic stress tolerance.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Ácido Ascórbico/metabolismo , Glutationa Transferase/genética , Reguladores de Crescimento de Plantas/metabolismo , Estresse Fisiológico/fisiologia , Ácido Abscísico/metabolismo , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/metabolismo , Ascorbato Oxidase/genética , Ascorbato Oxidase/metabolismo , Ácido Ascórbico/genética , Ciclopentanos/metabolismo , Galactose/farmacologia , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Glutationa Transferase/metabolismo , Ácidos Hexurônicos/metabolismo , Ácidos Indolacéticos/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/genética , Sesquiterpenos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
Biomolecules ; 11(6)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208762

RESUMO

Interactions between plant-associated fungi and their hosts are characterized by a continuous crosstalk of chemical molecules. Specialized metabolites are often produced during these associations and play important roles in the symbiosis between the plant and the fungus, as well as in the establishment of additional interactions between the symbionts and other organisms present in the niche. Serendipita indica, a root endophytic fungus from the phylum Basidiomycota, is able to colonize a wide range of plant species, conferring many benefits to its hosts. The genome of S. indica possesses only few genes predicted to be involved in specialized metabolite biosynthesis, including a putative terpenoid synthase gene (SiTPS). In our experimental setup, SiTPS expression was upregulated when the fungus colonized tomato roots compared to its expression in fungal biomass growing on synthetic medium. Heterologous expression of SiTPS in Escherichia coli showed that the produced protein catalyzes the synthesis of a few sesquiterpenoids, with the alcohol viridiflorol being the main product. To investigate the role of SiTPS in the plant-endophyte interaction, an SiTPS-over-expressing mutant line was created and assessed for its ability to colonize tomato roots. Although overexpression of SiTPS did not lead to improved fungal colonization ability, an in vitro growth-inhibition assay showed that viridiflorol has antifungal properties. Addition of viridiflorol to the culture medium inhibited the germination of spores from a phytopathogenic fungus, indicating that SiTPS and its products could provide S. indica with a competitive advantage over other plant-associated fungi during root colonization.


Assuntos
Alquil e Aril Transferases/isolamento & purificação , Basidiomycota/enzimologia , Sesquiterpenos/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Basidiomycota/metabolismo , Endófitos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Lycopersicon esculentum/metabolismo , Raízes de Plantas/metabolismo , Simbiose/genética , Terpenos/química , Terpenos/metabolismo
16.
Molecules ; 26(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203927

RESUMO

Artemisia ludoviciana subsp. mexicana has been traditionally used for the treatment of digestive ailments such as gastritis, whose main etiological agent is Helicobacter pylori. In a previous screening study, the aqueous extract exhibited a good in vitro anti-H. pylori activity. With the aim of determining the efficacy of this species as a treatment for H. pylori related diseases and finding bioactive compounds, its aqueous extract was subjected to solvent partitioning and the fractions obtained were tested for their in vitro anti-H. pylori effect, as well as for their in vivo gastroprotective and anti-inflammatory activities. The aqueous extract showed a MIC = 250 µg/mL. No acute toxicity was induced in mice. A gastroprotection of 69.8 ± 3.8%, as well as anti-inflammatory effects of 47.6 ± 12.4% and 38.8 ± 10.2% (by oral and topical administration, respectively), were attained. Estafiatin and eupatilin were isolated and exhibited anti-H. pylori activity with MBCs of 15.6 and 31.2 µg/mL, respectively. The finding that A. ludoviciana aqueous extract has significant anti-H. pylori, gastroprotective and anti-inflammatory activities is a relevant contribution to the ethnopharmacological knowledge of this species. This work is the first report about the in vivo gastroprotective activity of A. ludoviciana and the anti-H. pylori activity of eupatilin and estafiatin.


Assuntos
Artemisia/metabolismo , Flavonoides/farmacologia , Helicobacter pylori/efeitos dos fármacos , Animais , Antiulcerosos/farmacologia , Flavonoides/metabolismo , Gastrite/tratamento farmacológico , Masculino , Medicina Tradicional , Camundongos , Camundongos Endogâmicos , Extratos Vegetais/farmacologia , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Úlcera Gástrica/tratamento farmacológico
17.
J Agric Food Chem ; 69(26): 7334-7343, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34170670

RESUMO

The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is limited due to its cardiotoxicity. The aim of this study was to assess the possible cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced chronic cardiotoxicity and the underlying molecular mechanisms. DOX (2.5 mg/kg) was injected intraperitoneally once in a week for 5 weeks to induce chronic cardiotoxicity in male albino Wistar rats. The rats were treated with NERO (50 mg/kg, orally) 6 days a week for a duration of 5 weeks. DOX-injected rats showed a significant decline in cardiac function, elevated levels of serum cardiac marker enzymes, and enhanced oxidative stress markers along with altered PI3K/Akt and Nrf2/Keap1/HO-1 signaling pathways. DOX also triggered the activation of NF-κB/MAPK signaling and increased the levels/expression of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) and expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX activated NLRP3 inflammasome-mediated pyroptotic cell death along with fibrosis, mitochondrial dysfunction, DNA damage, and apoptosis in the myocardium. Additionally, histological studies, TUNEL staining, and myocardial lesions revealed structural alterations of the myocardium. NERO treatment showed considerable protective effects on the biochemical and molecular parameters studied. The findings demonstrate that NERO protects against DOX-induced chronic cardiotoxicity and the observed cardioprotective effects are attributed to its potent antioxidant and free radical scavenging properties.


Assuntos
Óleos Voláteis , Sesquiterpenos , Animais , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/toxicidade , Apoptose , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/metabolismo , Doxorrubicina/toxicidade , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Miocárdio/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Óleos Voláteis/farmacologia , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Wistar , Sesquiterpenos/metabolismo
18.
Nat Plants ; 7(6): 725-729, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34099902

RESUMO

Recent carbon dioxide (CO2) concentrations promoted higher parthenin concentrations in an invasive Parthenium hysterophorus biotype. Mean concentrations of parthenin, an allelopathic and defensive sesquiterpene lactone, were 49% higher at recent (~400 ppm) than at mid-twentieth-century (~300 ppm) CO2 concentrations, but did not vary in a non-invasive biotype, suggesting that recent increases in atmospheric CO2 may have already altered the chemistry of this destructive weed, potentially contributing to its invasive success.


Assuntos
Asteraceae/metabolismo , Dióxido de Carbono , Plantas Daninhas/metabolismo , Sesquiterpenos/metabolismo , Alelopatia , Asteraceae/fisiologia , Ecótipo , Espécies Introduzidas , Brotos de Planta/metabolismo , Plantas Daninhas/fisiologia , Toxinas Biológicas/metabolismo
19.
Microb Cell Fact ; 20(1): 89, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902586

RESUMO

BACKGROUND: Terpenes are remarkably diverse natural structures, which can be formed via two different pathways leading to two common intermediates. Among those, sesquiterpenes represent a variety of industrially relevant products. One important industrially produced product is ß-farnesene as a precursor for a jet fuel additive. So far, microbial terpene production has been mostly limited to known production hosts, which are only able to grow on heterotrophic substrates. RESULTS: In this paper, we for the first time describe ß-farnesene production by the versatile bacterial host Cupriavidus necator on fructose, which is known to grow hetero- and autotrophically and even in bioelectrochemical systems. We were able to show a growth-dependent production of ß-farnesene by expressing the ß-farnesene synthase from Artemisia annua in C. necator H16 PHB-4. Additionally, we performed a scale-up in a parallel reactor system with production titers of 26.3 ± 1.3 µM ß-farnesene with a fed-batch process. CONCLUSIONS: The ß-farnesene production titers reported in this paper are not in the same range as titers published with known heterotrophic producers E. coli or S. cerevisiae. However, this proof-of-principle study with C. necator as production host opens new synthesis routes toward a sustainable economy and leaves room for further optimizations, which have been already performed with the known production strains.


Assuntos
Cupriavidus necator/metabolismo , Engenharia Metabólica/métodos , Sesquiterpenos/metabolismo , Estudo de Prova de Conceito
20.
Molecules ; 26(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801899

RESUMO

Natural products are important sources for drug discovery, especially anti-tumor drugs. ß-Elemene, the prominent active ingredient extract from the rhizome of Curcuma wenyujin, is a representative natural product with broad anti-tumor activities. The main molecular mechanism of ß-elemene is to inhibit tumor growth and proliferation, induce apoptosis, inhibit tumor cell invasion and metastasis, enhance the sensitivity of chemoradiotherapy, regulate the immune system, and reverse multidrug resistance (MDR). Elemene oral emulsion and elemene injection were approved by the China Food and Drug Administration (CFDA) for the treatment of various cancers and bone metastasis in 1994. However, the lipophilicity and low bioavailability limit its application. To discover better ß-elemene-derived anti-tumor drugs with satisfying drug-like properties, researchers have modified its structure under the premise of not damaging the basic scaffold structure. In this review, we comprehensively discuss and summarize the potential anti-tumor mechanisms and the progress of structural modifications of ß-elemene.


Assuntos
Sesquiterpenos/química , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Anticarcinógenos/metabolismo , Anticarcinógenos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , China , Curcuma/metabolismo , Humanos , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/metabolismo , Sesquiterpenos Monocíclicos/farmacologia , Rizoma/metabolismo , Transdução de Sinais/efeitos dos fármacos
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