Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.813
Filtrar
1.
Nat Commun ; 11(1): 3958, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769971

RESUMO

Catalytic versatility is an inherent property of many enzymes. In nature, terpene cyclases comprise the foundation of molecular biodiversity as they generate diverse hydrocarbon scaffolds found in thousands of terpenoid natural products. Here, we report that the catalytic activity of the terpene cyclases AaTPS and FgGS can be switched from cyclase to aromatic prenyltransferase at basic pH to generate prenylindoles. The crystal structures of AaTPS and FgGS provide insights into the catalytic mechanism of this cryptic function. Moreover, aromatic prenyltransferase activity discovered in other terpene cyclases indicates that this cryptic function is broadly conserved among the greater family of terpene cyclases. We suggest that this cryptic function is chemoprotective for the cell by regulating isoprenoid diphosphate concentrations so that they are maintained below toxic thresholds.


Assuntos
Dimetilaliltranstransferase/metabolismo , Liases Intramoleculares/metabolismo , Alternaria/enzimologia , Domínio Catalítico , Dimetilaliltranstransferase/química , Ensaios Enzimáticos , Escherichia coli/metabolismo , Fusarium/enzimologia , Indóis/química , Indóis/metabolismo , Liases Intramoleculares/química , Cinética , Ligantes , Modelos Moleculares , Prenilação , Terpenos/metabolismo
2.
Nature ; 584(7819): 75-81, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760044

RESUMO

Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C-N coupling protocol by preparing commercial medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks.


Assuntos
Compostos de Anilina/síntese química , Hidrogênio/química , Processos Fotoquímicos , Aminação , Aminas/química , Compostos de Anilina/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Catálise/efeitos da radiação , Cicloexanonas/química , Oxirredução/efeitos da radiação , Processos Fotoquímicos/efeitos da radiação , Esteroides/síntese química , Esteroides/química , Terpenos/síntese química , Terpenos/química
4.
Plant Mol Biol ; 104(1-2): 203-215, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32683610

RESUMO

KEY MESSAGE: Distinct catalytic features of the Poaceae TPS-a subfamily arose early in grass evolution and the reactions catalyzed have become more complex with time. The structural diversity of terpenes found in nature is mainly determined by terpene synthases (TPS). TPS enzymes accept ubiquitous prenyl diphosphates as substrates and convert them into the various terpene skeletons by catalyzing a carbocation-driven reaction. Based on their sequence similarity, terpene synthases from land plants can be divided into different subfamilies, TPS-a to TPS-h. In this study, we aimed to understand the evolution and functional diversification of the TPS-a subfamily in the Poaceae (the grass family), a plant family that contains important crops such as maize, wheat, rice, and sorghum. Sequence comparisons showed that aside from one clade shared with other monocot plants, the Poaceae TPS-a subfamily consists of five well-defined clades I-V, the common ancestor of which probably originated very early in the evolution of the grasses. A survey of the TPS literature and the characterization of representative TPS enzymes from clades I-III revealed clade-specific substrate and product specificities. The enzymes in both clade I and II function as sesquiterpene synthases with clade I enzymes catalyzing initial C10-C1 or C11-C1 ring closures and clade II enzymes catalyzing C6-C1 closures. The enzymes of clade III mainly act as monoterpene synthases, forming cyclic and acyclic monoterpenes. The reconstruction and characterization of clade ancestors demonstrated that the differences among clades I-III were already present in their ancestors. However, the ancestors generally catalyzed simpler reactions with less double-bond isomerization and fewer cyclization steps. Overall, our data indicate an early origin of key enzymatic features of TPS-a enzymes in the Poaceae, and the development of more complex reactions over the course of evolution.


Assuntos
Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Poaceae/enzimologia , Poaceae/genética , Alquil e Aril Transferases/classificação , Clonagem Molecular , Escherichia coli/genética , Evolução Molecular , Genes de Plantas/genética , Liases Intramoleculares/metabolismo , Proteínas de Plantas/genética , Análise de Sequência , Terpenos/metabolismo
5.
J Laryngol Otol ; 134(7): 571-576, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32605666

RESUMO

BACKGROUND: An objective evaluation of coronavirus disease 2019 in the first days of infection is almost impossible, as affected individuals are generally in home quarantine, and there is limited accessibility for the operator who should perform the test. To overcome this limitation, a recently validated psychophysical self-administered test was used, which can be performed remotely in the assessment of early-stage coronavirus disease 2019 patients. METHODS: Olfactory and gustatory functions were objectively assessed in 300 patients in the first 7 days from coronavirus disease 2019 symptom onset. RESULTS: Seventy per cent of the patients presented olfactory and/or gustatory disorders. The dysfunctions detected were mainly complete anosmia (47 per cent) or ageusia (38 per cent). A significant correlation was found between taste dysfunction and female gender (odds ratio = 1.936, p = 0.014) and fever (odds ratio = 2.132, p = 0.003). CONCLUSION: The psychophysical evaluation protocol proposed is an effective tool for the fast and objective evaluation of patients in the early stages of coronavirus disease 2019. Chemosensitive disorders have been confirmed to be frequent and early symptoms of the coronavirus infection, and, in a significant number of cases, they are the first or only manifestation of coronavirus disease 2019.


Assuntos
Infecções por Coronavirus/fisiopatologia , Autoavaliação Diagnóstica , Técnicas e Procedimentos Diagnósticos , Transtornos do Olfato/diagnóstico , Pneumonia Viral/fisiopatologia , Distúrbios do Paladar/diagnóstico , Telemedicina , Ácido Acético , Adulto , Betacoronavirus , Chocolate , Café , Combinação de Medicamentos , Feminino , Sucos de Frutas e Vegetais , Produtos Domésticos , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais , Transtornos do Olfato/fisiopatologia , Pandemias , Extratos Vegetais , Autorrelato , Limiar Sensorial , Fatores Sexuais , Sabões , Especiarias , Distúrbios do Paladar/fisiopatologia , Limiar Gustativo , Terpenos , Cremes Dentais , Vinho
6.
Gene ; 758: 144961, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32693148

RESUMO

Ginkgo biloba L. is regarded as the most ancient living tree, and its kernel has been used as a traditional Chinese medicine for more than 2,000 years. The leaf extracts of this tree have been among the bestselling herbal remedies in Western countries since the last century. To understand the biosynthesis of the pharmacologically active ingredients in G. biloba, flavonoids and terpenoid trilactones (TTLs), we sequenced the transcriptomes of G. biloba leaves, kernels and testae with Iso-Seq and RNA-Seq technologies and obtained 152,524 clean consensus reads. When these reads were used to improve the annotation of the G. biloba genome, 4,856 novel genes, 25,583 new isoforms of previously annotated genes and 4,363 lncRNAs were discovered. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that genes involved in growth, regulation and response to stress were more likely to be regulated by alternative splicing (AS) or alternative polyadenylation (APA), which represent the two most important posttranscriptional regulation mechanisms. It was found that some of the characterized genes involved in the biosynthesis of flavonoids and TTLs were also possibly regulated by AS and APA. Using phylogenetic and gene expression pattern analyses, some candidate genes for the biosynthesis of flavonoids and TTLs were screened. After qRT-PCR validation, the final candidate genes for flavonoid biosynthesis included three UDP-glycosyltransferases and one MYB transcription factor, while the candidate genes for TTL biosynthesis included two cytochrome P450 and one WRKY transcription factor. Our study suggested that Iso-Seq may play an important role in improving genome annotation, elucidating AS and APA mechanisms and discovering candidate genes involved in the biosynthesis of some secondary metabolites.


Assuntos
Flavonoides/biossíntese , Regulação da Expressão Gênica de Plantas/genética , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Lactonas/metabolismo , Terpenos/metabolismo , Processamento Alternativo/genética , Sistema Enzimático do Citocromo P-450/genética , Perfilação da Expressão Gênica , Genoma de Planta/genética , Extratos Vegetais , Transcriptoma , Sequenciamento Completo do Genoma
7.
Bull Environ Contam Toxicol ; 105(2): 230-236, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32671410

RESUMO

Fifty-four surface sediments from the typical coal mining area were analyzed for pristane, phytane and C8-C40 n-alkanes using gas chromatography-mass spectrometry (GC-MS). The spatial distribution, homolog profiles and source apportionment of aliphatic hydrocarbons were investigated. Bimodal distribution pattern, centered at C16-C20 and C27-C33 n-alkanes, were observed in all sediment samples with an obvious dominance of low molecular weight homologues. Principal component analysis-multiple linear regression (PCA-MLR) was used to predict the contributions of different sources. The result implied that natural input was the main source, contribution of which accounted for 60.8%, and the contributions of different sources were estimated as follow: 21.8% for terrestrial higher plants, 24.1% for algae and photosynthetic bacteria, 14.9% for submerged/floating macrophytes, 23.5% for fossil fuel combustion and 15.7% for petroleum hydrocarbons. Moreover, relatively high median concentrations of fossil fuel combustion were observed in Shou County and Fengtai County, indicating the high contribution of fossil fuel combustion in these two areas.


Assuntos
Minas de Carvão , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Hidrocarbonetos/análise , Petróleo/análise , Alcanos/análise , China , Diterpenos/análise , Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos Policíclicos Aromáticos/análise , Análise de Componente Principal , Terpenos/análise , Poluentes Químicos da Água/análise
8.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1545-1557, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489033

RESUMO

An ultra-performance liquid chromatography(UPLC) method integrating characteristic chromatogram and eight terpenoids determination has been established for comparing the differences of Alismatis Rhizoma(Zexie) from different product areas. Thirty-seven batches of crude drugs and thirty batches of prepared slices of Alismatis Rhizoma were analyzed. The obtained data were analyzed by similarity evaluation, principal components analysis(PCA) and partial least squares discriminant analysis(PLS-DA). There were three main characteristic peaks in the characteristic chromatograms, and alisol B 23-acetate(S) was selected as the reference. Compared with the S peak, the relative retention times of the other two characteristic peaks were 0.55(alisol) and 0.77(alisol B), respectively. Peak areas and the ratio of alisol B to alisol B 23-acetate could be used to distinguish Alismatis Rhizoma from different geographical origins. The samples were divided into three groups by PCA and PLS-DA based on the content determination results, and they were "Jian Zexie"(Fujian and Jiangxi provinces), "Chuan Zexie"(Sichuan and Hubei provinces), and "Guang Zexie"(Guangxi province). The contents of chemical components in samples from different producing areas were notably different. For example, the contents of alisol A and alisol A 24-acetate were significantly higher in "Guang Zexie" compared with "Jian Zexie" and "Chuan Zexie"(P<0.000 1). The contents of alisol B and alisol C were significantly higher in "Chuan Zexie" compared with "Jian Zexie"(P<0.000 1). Combining the characteristic chromatograms and quantitative analysis of eight terpenoids, this study showed that the relative contents of components and their ratios were notable different in samples from different regions, but types and numbers of chemical compositions were basically similar. The results of this study illustrated the regional differences of Alismatis Rhizoma and their components characteristics, and provided references for authentication and quality control of Alismatis Rhizoma.


Assuntos
Rizoma , China , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Terpenos
9.
Braz Oral Res ; 34: e050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578760

RESUMO

Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - terpinen-4-ol - against resistant Candida albicans strains (genotypes A and B) identified by molecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell proliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of terpinen-4-ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and terpinen-4-ol present promising results for the treatment of oral candidiasis.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Óleo de Melaleuca/farmacologia , Terpenos/farmacologia , Resinas Acrílicas , Análise de Variância , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Bases de Dentadura/microbiologia , Testes de Sensibilidade Microbiana , Microscopia Confocal , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Óleo de Melaleuca/química , Terpenos/química
10.
J Chromatogr A ; 1624: 461191, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32540059

RESUMO

Trapping volatiles is a convenient way to study aroma compounds but it is important to determine which volatile trapping method is most comprehensive in extracting the most relevant aroma components when investigating complex food products. Awareness of their limitations is also crucial. (Un)targeted metabolomic approaches were used to determine the volatile profiles of two commercial flavourings. Four trapping techniques were tested as was the addition of salt to the mixture. Comprehensiveness and repeatability were compared and SBSE proved particularly suitable for extracting components such as polysulfides, pyrazines and terpene alcohols, and provided an overall broader chemical spectrum. SPME proved to be more suitable in extracting sesquiterpenes and DHS in extracting monoterpenes. Adding salt to the sample had only quantitative effects on volatiles as detected by SPME. These results help clarify the advantages and limitations of different trapping techniques and hence deliver a valuable decision tool for food matrix analysis.


Assuntos
Aromatizantes/análise , Cromatografia Gasosa-Espectrometria de Massas , Aromatizantes/química , Aromatizantes/isolamento & purificação , Metabolômica , Monoterpenos/isolamento & purificação , Odorantes , Pirazinas/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Microextração em Fase Sólida/métodos , Sulfetos/isolamento & purificação , Terpenos/isolamento & purificação , Compostos Orgânicos Voláteis/análise
11.
PLoS One ; 15(5): e0231948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369483

RESUMO

In our search for bioactive mushrooms native to British Columbia, we determined that the ethanol extracts from fruiting bodies of the terrestrial polypore Albatrellus flettii had potent anti-cell viability activity. Using bioassay-guided fractionation, mass spectrometry and nuclear magnetic resonance, we successfully isolated three known compounds (grifolin, neogrifolin and confluentin). These compounds represent the major anti-cell viability components from the ethanol extracts of A. flettii. We also identified a novel biological activity for these compounds, specifically in down-regulating KRAS expression in two human colon cancer cell lines. Relatively little is known about the anti-cell viability activity and mechanism of action of confluentin. For the first time, we show the ability of confluentin to induce apoptosis and arrest the cell cycle at the G2/M phase in SW480 human colon cancer cells. The oncogenic insulin-like growth factor 2 mRNA-binding protein 1 (IMP1) has been previously shown to regulate KRAS mRNA expression in colon cancer cells, possibly through its ability to bind to the KRAS transcript. Using a fluorescence polarization assay, we show that confluentin dose-dependently inhibits the physical interaction between KRAS RNA and full-length IMP1. The inhibition also occurs with truncated IMP1 containing the KH1 to KH4 domain (KH1to4 IMP1), but not with the di-domain KH3 and KH4 (KH3&4 IMP1). In addition, unlike the control antibiotic neomycin, grifolin, neogrifolin and confluentin do not bind to KRAS RNA. These results suggest that confluentin inhibits IMP1-KRAS RNA interaction by binding to the KH1&2 di-domains of IMP1. Since the molecular interaction between IMP1 and its target RNAs is a pre-requisite for the oncogenic function of IMP1, confluentin should be further explored as a potential inhibitor of IMP1 in vivo.


Assuntos
Basidiomycota/química , Neoplasias do Colo/genética , Fenóis/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Resorcinóis/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Terpenos/farmacologia
12.
PLoS One ; 15(4): e0232220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353014

RESUMO

Terpenes are the largest class of natural products with extensive structural diversity and are widely used as pharmaceuticals, herbicides, flavourings, fragrances, and biofuels. While they have mostly been isolated from plants and fungi, the availability and analysis of bacterial genome sequence data indicates that bacteria also possess many putative terpene synthase genes. In this study, we further explore this potential for terpene synthase activity in bacteria. Twenty two potential class I terpene synthase genes (TSs) were selected to represent the full sequence diversity of bacterial synthase candidates and recombinantly expressed in E. coli. Terpene synthase activity was detected for 15 of these enzymes, and included mono-, sesqui- and diterpene synthase activities. A number of confirmed sesquiterpene synthases also exhibited promiscuous monoterpene synthase activity, suggesting that bacteria are potentially a richer source of monoterpene synthase activity then previously assumed. Several terpenoid products not previously detected in bacteria were identified, including aromandendrene, acora-3,7(14)-diene and longiborneol. Overall, we have identified promiscuous terpene synthases in bacteria and demonstrated that terpene synthases with substrate promiscuity are widely distributed in nature, forming a rich resource for engineering terpene biosynthetic pathways for biotechnology.


Assuntos
Alquil e Aril Transferases/genética , Bactérias/genética , Vias Biossintéticas/genética , Genoma Bacteriano/genética , Filogenia , Terpenos/metabolismo
13.
Planta Med ; 86(9): 643-654, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32365391

RESUMO

As part of our ongoing search for antiprotozoal natural products from plants, we examined different resins from the Burseraceae family. The dichloromethane extract obtained from myrrh, the oleo-gum-resin of Commiphora species, showed promising in vitro activity against Plasmodium falciparum with an IC50 value of 1 µg/mL. Bioactivity-guided fractionation led to the isolation and characterization of 18 sesquiterpenoids, namely, ß-elemene (1: ), elemyl acetate (2: ), curzerenone (3: ), 8-hydroxyisogermafurenolide (4: ), 2-methoxyisogermafurenolide (5: ), 8-epi-2-methoxyisogermafurenolide (6: ), furanodienone (7: ), 1(10)Z,4Z-furanodien-6-one (8: ), rel-2R-methyl-5S-acetoxy-4R-furanogermacr-1(10)Z-en-6-one (9: ), (1(10)E)-2-methoxy-8,12-epoxygermacra-1(10),7,11-trien-6-one (10: ), 2R-methoxyfuranodiene (11: ), 2-acetyloxyglechomanolide (12: ), 8-epi-2-acetyloxyglechomanolide (13: ), (1R,2R,4S)-1,2-epoxyfuranogermacr-10(15)-en-6-one (14: ), hydroxylindestrenolide (15: ), isohydroxylindestrenolide (16: ), myrrhone (17: ), and myrrhterpenoid O (18: ). Moreover, nine (nor-)triterpenoids were isolated: mansumbinol (19: ), mansumbinol epoxide (20: ), mansumbinone (21: ), mansumbin-13(17)-en-3,16-dione (22: ), 3,4-seco-mansumbinoic acid (23: ), rel-20S-hydroxy-dammar-24-en-3,16-dione (24: ), rel-(16S,20S)-dihydroxydammar-24-en-3-one (25: ), cycloart-24-en-1α,2α,3ß-triol (26: ), and 3ß-isovaleroyloxycycloart-24-en-1α,2α-diol (27: ). All compounds were identified by MS and NMR spectroscopic analyses. To the best of our knowledge, compounds 5, 6, 12, 13, 16, 18: , and 20: are reported for the first time. All isolated compounds were tested in vitro for activity against P. falciparum and cytotoxicity. The sesquiterpene 7: and the triterpene 25: were the most active compounds found in this study with IC50 values of 7.4 and 2.8 µM, respectively.


Assuntos
Antimaláricos , Commiphora , Extratos Vegetais , Resinas Vegetais , Terpenos
14.
Biotechnol Adv ; 41: 107550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32360984

RESUMO

Flavonoids, terpenoids, and polyketides are structurally diverse secondary metabolites used widely as pharmaceuticals and nutraceuticals. Most of these molecules exist in nature as glycosides, in which sugar residues act as a decisive factor in their architectural complexity and bioactivity. Engineering glycosylation through selective trimming or extension of the sugar residues in these molecules is a prerequisite to their commercial production as well to creating novel derivatives with specialized functions. Traditional chemical glycosylation methods are tedious and can offer only limited end-product diversity. New in vitro and in vivo biocatalytic tools have emerged as outstanding platforms for engineering glycosylation in these three classes of secondary metabolites to create a large repertoire of versatile glycoprofiles. As knowledge has increased about secondary metabolite-associated promiscuous glycosyltransferases and sugar biosynthetic machinery, along with phenomenal progress in combinatorial biosynthesis, reliable industrial production of unnatural secondary metabolites has gained momentum in recent years. This review highlights the significant role of sugar residues in naturally occurring flavonoids, terpenoids, and polyketide antibiotics. General biocatalytic tools used to alter the identity and pattern of sugar molecules are described, followed by a detailed illustration of diverse strategies used in the past decade to engineer glycosylation of these valuable metabolites, exemplified with commercialized products and patents. By addressing the challenges involved in current bio catalytic methods and considering the perspectives portrayed in this review, exceptional drugs, flavors, and aromas from these small molecules could come to dominate the natural-product industry.


Assuntos
Flavonoides , Policetídeos , Antibacterianos , Glicosilação , Glicosiltransferases , Terpenos
15.
Phytochemistry ; 176: 112403, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32422392

RESUMO

Prostanthera lasianthos (Lamiaceae) is commonly referred to as the 'Victorian Christmas Bush', a name that derives from the floral display it gives in the Christmas period. However, botanists recognise P. lasianthos as a heterogeneous species aggregate that includes several putative new species that are confined to disjunct locations. Recently one taxon was revised to P. eungella B.J.Conn & K.M.Proft. In the current study the chemistry of essential oils was determined for 25 specimens, representative of 8 taxa (including P. eungella). Chemical relationships were investigated using two types of multivariate analysis and several distinct chemical profiles were identified. One taxon (P. sp. Wollomombi Gorge) was sampled nine times from three different locations during the year to determine the effects of seasonal variation and subjectively-assessed soil moisture content. It was demonstrated that the chemistry of this taxon is strongly influenced by soil moisture independently of growth stage, but possibly influenced by periods of dry or wet weather. Two distinct chemotypes and one intermediate type were identified. These chemotypes differed by mediated expression of linalool and hence linalyl acetate. These metabolites were also present in specimens of P. sp. Bald Mountain, but as minor components. This latter taxon could be reliably distinguished by higher relative abundance of butanoic acid, 1-methylbutyl ester. As judged by a smaller sampling size for the other taxa, evidence that this pattern of mediated expression between terpene species was found. However, the identity of terpenes that demonstrated this mediated expression were different for each taxon; for example, volatiles from P. eungella demonstrated mediation between α-pinene and caryophyllene. Nevertheless, it is possible that chemical expression of all taxa in the heterogeneous species aggregate is strongly mediated by the moisture or nutrient content of soils. Thus, the dataset produced during this study can be used as a reference against other chemical data to investigate taxonomic placement in members of this group.


Assuntos
Lamiaceae , Óleos Voláteis , Adaptação Fisiológica , Austrália , Terpenos
16.
Food Chem ; 324: 126903, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32361095

RESUMO

Cuticular wax chemicals differ among fruit cultivars and contribute to storage ability. However, wax analysis in apple cultivars, particularly during storage, has not been described. In this work, the chemicals and crystal structures of cuticular wax in 10 apple cultivars were analyzed to observe wax functions in apple during storage. Results showed that alkanes and primary alcohols decreased while fatty acids increased in stored fruits of all cultivars compared with the fruits before storage. Terpenoids, aldehydes, and phenols were observed in stored fruits but not in the fruits before storage in all cultivars except 'Red Star' fruit. The weight loss rate was significantly correlated with six components including C13 alcohol, C14 alkanes, total alkanes, total wax, C13 alkanes and C54 alkanes in 10 cultivar apple fruits during storage. Our findings indicate that the total wax, particularly alkanes, in the peel of apple fruits is essential for storage and quality control.


Assuntos
Armazenamento de Alimentos/métodos , Malus/química , Ceras/química , Álcoois/metabolismo , Aldeídos/análise , Alcanos/metabolismo , Ácidos Graxos/metabolismo , Frutas/química , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Malus/metabolismo , Fenóis/análise , Terpenos/análise , Ceras/análise
17.
Phytochemistry ; 174: 112341, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32240851

RESUMO

Eight undescribed terpenoids, namely, odongrossins A-H, together with two known terpenoids were isolated from Odontoschisma grosseverrucosum Stephani (Cephaloziaceae). Their structures were established based on NMR data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction measurements. Odongrossin A and odongrossin G displayed moderate anti-virulence activities against CDR1-and CDR2-efflux-pump-deficient Candida albicans DSY654. Further investigation of odongrossin A revealed that it inhibited adhesion and biofilm formation on C. albicans DSY654. The results regarding the transcription levels of genes demonstrated that odongrossin A could regulate the expression of genes that are associated with the virulence of C. albicans DSY654.


Assuntos
Antifúngicos , Hepatófitas , Biofilmes , Candida albicans , Proteínas Fúngicas , Terpenos , Virulência
18.
PLoS Comput Biol ; 16(4): e1007799, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32287281

RESUMO

13C-metabolic flux analysis (13C-MFA) allows metabolic fluxes to be quantified in living organisms and is a major tool in biotechnology and systems biology. Current 13C-MFA approaches model label propagation starting from the extracellular 13C-labeled nutrient(s), which limits their applicability to the analysis of pathways close to this metabolic entry point. Here, we propose a new approach to quantify fluxes through any metabolic subnetwork of interest by modeling label propagation directly from the metabolic precursor(s) of this subnetwork. The flux calculations are thus purely based on information from within the subnetwork of interest, and no additional knowledge about the surrounding network (such as atom transitions in upstream reactions or the labeling of the extracellular nutrient) is required. This approach, termed ScalaFlux for SCALAble metabolic FLUX analysis, can be scaled up from individual reactions to pathways to sets of pathways. ScalaFlux has several benefits compared with current 13C-MFA approaches: greater network coverage, lower data requirements, independence from cell physiology, robustness to gaps in data and network information, better computational efficiency, applicability to rich media, and enhanced flux identifiability. We validated ScalaFlux using a theoretical network and simulated data. We also used the approach to quantify fluxes through the prenyl pyrophosphate pathway of Saccharomyces cerevisiae mutants engineered to produce phytoene, using a dataset for which fluxes could not be calculated using existing approaches. A broad range of metabolic systems can be targeted with minimal cost and effort, making ScalaFlux a valuable tool for the analysis of metabolic fluxes.


Assuntos
Análise do Fluxo Metabólico/métodos , Redes e Vias Metabólicas/fisiologia , Modelos Biológicos , Isótopos de Carbono/análise , Isótopos de Carbono/metabolismo , Engenharia Metabólica , Fosfatos de Poli-Isoprenil/metabolismo , Saccharomyces cerevisiae/metabolismo , Biologia de Sistemas , Terpenos/metabolismo
19.
Plant Mol Biol ; 103(4-5): 489-505, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32306368

RESUMO

KEY MESSAGE: Cucumber plants adapt their transcriptome and metabolome as result of spider mite infestation with opposite consequences for direct and indirect defences in two genotypes. Plants respond to arthropod attack with the rearrangement of their transcriptome which lead to subsequent phenotypic changes in the plants' metabolome. Here, we analysed transcriptomic and metabolite responses of two cucumber (Cucumis sativus) genotypes to chelicerate spider mites (Tetranychus urticae) during the first 3 days of infestation. Genes associated with the metabolism of jasmonates, phenylpropanoids, terpenoids and L-phenylalanine were most strongly upregulated. Also, genes involved in the biosynthesis of precursors for indirect defence-related terpenoids were upregulated while those involved in the biosynthesis of direct defence-related cucurbitacin C were downregulated. Consistent with the observed transcriptional changes, terpenoid emission increased and cucurbitacin C content decreased during early spider-mite herbivory. To further study the regulatory network that underlies induced defence to spider mites, differentially expressed genes that encode transcription factors (TFs) were analysed. Correlation analysis of the expression of TF genes with metabolism-associated genes resulted in putative identification of regulators of herbivore-induced terpenoid, green-leaf volatiles and cucurbitacin biosynthesis. Our data provide a global image of the transcriptional changes in cucumber leaves in response to spider-mite herbivory and that of metabolites that are potentially involved in the regulation of induced direct and indirect defences against spider-mite herbivory.


Assuntos
Cucumis sativus/imunologia , Cucumis sativus/metabolismo , Metaboloma , Infestações por Ácaros/imunologia , Infestações por Ácaros/metabolismo , Tetranychidae , Transcriptoma , Animais , Vias Biossintéticas/genética , Cucumis sativus/genética , Cucumis sativus/parasitologia , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Genoma de Planta , Genótipo , Herbivoria , Oxilipinas/metabolismo , Fenilalanina/metabolismo , Fenilpropionatos/metabolismo , Doenças das Plantas , Folhas de Planta/metabolismo , Metabolismo Secundário/genética , Terpenos/metabolismo , Fatores de Transcrição/genética , Triterpenos/metabolismo , Compostos Orgânicos Voláteis/metabolismo
20.
Am J Physiol Renal Physiol ; 318(5): F1258-F1270, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32249615

RESUMO

B lymphocyte hyperactivity plays a pathogenic role in systemic lupus erythematosus (SLE), and spliced X box-binding protein 1 (XBP1s) has been implicated in B cell maturation and differentiation. We hypothesized that blockade of the XBP1s pathway inhibits the B cell hyperactivity underlying SLE and lupus nephritis (LN) development. In the present study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. The lupus mouse model was successfully established, as indicated by the presence of LN with markedly increased urine protein levels, renal deposition of Ig, and mesangial cell proliferation. In lupus mice, B cell hyperactivity was confirmed by increased CD40 and B cell-activating factor levels. B cell activation and plasma cell overproduction were determined by increases in CD40-positive and CD138-positive cells in the spleens of lupus mice by flow cytometry and further confirmed by CD45R and Ig light chain staining in the splenic tissues of lupus mice. mRNA and protein expression of XBP1s in B cells was assessed by real-time PCR, Western blot analysis, and immunofluorescence analysis and was increased in lupus mice. In addition, almost all changes were reversed by STF083010 treatment. However, the expression of XBP1s in the kidneys did not change when mice were exposed to pristane and STF083010. Taken together, these findings suggest that expression of XBP1s in B cells plays key roles in SLE and LN development. Blockade of the XBP1s pathway may be a potential strategy for SLE and LN treatment.


Assuntos
Linfócitos B/metabolismo , Rim/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/metabolismo , Ativação Linfocitária , Baço/metabolismo , Terpenos , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Autoanticorpos/sangue , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Imunoglobulina G/sangue , Rim/efeitos dos fármacos , Rim/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Baço/efeitos dos fármacos , Baço/patologia , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Proteína 1 de Ligação a X-Box/antagonistas & inibidores , Proteína 1 de Ligação a X-Box/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA