Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field

Ferulic acid is a phenolic acid widely distributed in the plant kingdom. It presents a wide range of potential therapeutic effects useful in the treatments of cancer, diabetes, lung and cardiovascular diseases, as well as hepatic, neuro and photoprotective effects and antimicrobial and anti-inflammatory activities. Overall, the pharmaceutical potential of ferulic acid can be attributed to its ability to scavenge free radicals. However, recent studies have revealed that ferulic acid presents pharmacological properties beyond those related to its antioxidant activity, such as the ability to competitively inhibit HMG-CoA reductase and activate glucokinase, contributing to reduce hypercholesterolemia and hyperglycemia, respectively. The present review addresses ferulic acid dietary sources, the pharmacokinetic profile, antioxidant action mechanisms and therapeutic effects in the treatment and prevention of various diseases, in order to provide a basis for understanding its mechanisms of action as well as its pharmaceutical potential.O ácido ferúlico é um ácido fenólico amplamente distribuído no reino vegetal. Ele apresenta uma ampla gama de potenciais efeitos terapêuticos utéis no tratamento do câncer, diabetes, doenças pulmonares e cardiovasculares, bem como efeitos hepáticos, neuro e fotoprotetores, atividades antimicrobianas e anti-inflamatórias. O potencial farmacêutico do ácido ferúlico pode ser atribuído à sua capacidade em sequestrar radicais livres. No entanto, estudos recentes revelaram que o ácido ferúlico apresenta propriedades farmacológicas, além da sua atividade antioxidante, como a capacidade de inibir competitivamente a HMG-CoA redutase e ativar a glucoquinase, contribuindo para reduzir a hipercolesterolemia e hiperglicemia, respectivamente. A presente revisão aborda as fontes dietéticas de ácido ferúlico, o perfil farmacocinético, os mecanismos de ação como antioxidante e efeitos terapêuticos no tratamento e prevenção de várias doenças, de modo a proporcionar uma base para a compreensão dos seus mecanismos de ação, bem como os seus potenciais farmacêuticos

Heterologous expression and functional characterization of a GH10 endoxylanase from \u3ci\u3eAspergillus fumigatus\u3c/i\u3e var. \u3ci\u3eniveus\u3c/i\u3e with potential biotechnological application

Xylanases decrease the xylan content in pretreated biomass releasing it from hemicellulose, thus improving the accessibility of cellulose for cellulases. In this work, an endo-β-1,4-xylanase from Aspergillus fumigatus var. niveus (AFUMN-GH10) was successfully expressed. The structural analysis and biochemical characterization showed this AFUMN-GH10 does not contain a carbohydrate-binding module. The enzyme retained its activity in a pH range from 4.5 to 7.0, with an optimal temperature at 60°C. AFUMN-GH10 showed the highest activity in beechwood xylan. The mode of action of AFUMNGH10 was investigated by hydrolysis of APTS-labeled xylohexaose, which resulted in xylotriose and xylobiose as the main products. AFUMN-GH10 released 27% of residual xylan from hydrothermally-pretreated corn stover and 14% of residual xylan from hydrothermally-pretreated sugarcane bagasse. The results showed that environmentally friendly pretreatment followed by enzymatic hydrolysis with AFUMN-GH10 in low concentration is a suitable method to remove part of residual and recalcitrant hemicellulose from biomass

Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

AbstractEndo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the −1 and −2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20°C, and exclusively xylobiose at 90°C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures

Heterologous expression and functional characterization of a GH10 endoxylanase from \u3ci\u3eAspergillus fumigatus\u3c/i\u3e var. \u3ci\u3eniveus\u3c/i\u3e with potential biotechnological application

Xylanases decrease the xylan content in pretreated biomass releasing it from hemicellulose, thus improving the accessibility of cellulose for cellulases. In this work, an endo-β-1,4-xylanase from Aspergillus fumigatus var. niveus (AFUMN-GH10) was successfully expressed. The structural analysis and biochemical characterization showed this AFUMN-GH10 does not contain a carbohydrate-binding module. The enzyme retained its activity in a pH range from 4.5 to 7.0, with an optimal temperature at 60°C. AFUMN-GH10 showed the highest activity in beechwood xylan. The mode of action of AFUMNGH10 was investigated by hydrolysis of APTS-labeled xylohexaose, which resulted in xylotriose and xylobiose as the main products. AFUMN-GH10 released 27% of residual xylan from hydrothermally-pretreated corn stover and 14% of residual xylan from hydrothermally-pretreated sugarcane bagasse. The results showed that environmentally friendly pretreatment followed by enzymatic hydrolysis with AFUMN-GH10 in low concentration is a suitable method to remove part of residual and recalcitrant hemicellulose from biomass

Cloning, expression, purification, crystallization and preliminary X-ray diffraction studies of the catalytic domain of a hyperthermostable endo-1,4-B-D-mannanase from Thermotoga petrophila RKU-1

Endo-1,4-[beta]-D-mannanases play key roles in seed germination and fruit ripening and have recently received much attention owing to their potential applications in the food, detergent and kraft pulp industries. In order to delineate their structural determinants for specificity and stability, X-ray crystallographic investigations combined with detailed functional studies are being performed. In this work, crystals of the catalytic domain of a hyperthermostable endo-1,4-[beta]-D-mannanase from Thermotoga petrophila RKU-1 were obtained from three different conditions, resulting in two crystalline forms. Crystals from conditions with phosphate or citrate salts as precipitant (CryP) belonged to space group P212121, with unit-cell parameters a = 58.76, b = 87.99, c = 97.34 A, while a crystal from a condition with ethanol as precipitant (CryE) belonged to space group I212121, with unit-cell parameters a = 91.03, b = 89.97, c = 97.89 A. CryP and CryE diffracted to resolutions of 1.40 and 1.45 A, respectively.Peer reviewedMicrobiology and Molecular Genetic

Estudos com carotenoides de leveduras do genero Rhodotorula : desenvolvimento de metodo analitico, influencia de inibidores e cultivo em meio alternativo a base de caldo de cana-de-açucar

Orientador: Adriana Zerlotti MercadanteDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de AlimentosResumo: Os carotenóides compõem um grupo de pigmentos naturais amplamente distribuídos na natureza com grande diversidade de estruturas e funções. O interesse pelos carotenóides tem aumentado onsideravelmente nos últimos anos, havendo uma potencial demanda por fontes naturais destes compostos nas indústrias de alimentos, farmacêutica e cosmética. As principais fontes industriais de carotenóides são a síntese química e a extração a partir de plantas, porém são poucos os carotenóides que possuem métodos economicamente eficientes de produção. Atualmente, apesar do pequeno número de carotenóides produzidos por biossíntese microbiana, esforços têm sido direcionados no desenvolvimento de processos biotecnológicos para a sua produção. Os carotenóides em microrganismos estão localizados intracelularmente, portanto além de uma elevada quantidade de carotenóides, os organismos selecionados para o desenvolvimento de processos biotecnológicos devem apresentar outras possibilidades, como o cultivo em resíduos ou substratos de baixo custo, produção de carotenóides com alto valor agregado, ou de outros compostos de interesse comercial, como ácidos graxas insaturados ou polissacarídeos. A primeira etapa deste trabalho foi o desenvolvimento de uma metodologia para extração e separação dos carotenóides de Rhodotorula rubra, R. glutinis, R. araucariae, R. minuta e R. lactosa. Dos métodos de extração testados, a utilização de areia tratada como agente abrasivo para o rompimento da parede celular e liberação dos carotenóides, apresentou grande eficiência ¿Observação: O resumo, na íntegra poderá ser visualizado no texto completo da tese digital.Abstract: Not informed.MestradoMestre em Ciência de Alimento

Expression, purification, crystallization and preliminary crystallographic analysis of an endo-1,5-α-l-arabinanase from hyperthermophilic Thermotoga petrophila

The crystallization and preliminary X-ray diffraction studies of an endo-1,5-α-arabinanase from hyperthermophilic T. petrophila are reported. The crystals diffracted to 2.86 Å resolution

Discovery, structural characterization, and functional insights into a novel apiosidase from the GH140 family, isolated from a lignocellulolytic-enriched mangrove microbial community

OBJECTIVES: Apiosidases are enzymes that cleave the glycosidic bond between the monosaccharides linked to apiose, a branched chain furanose found in the cell walls of vascular plants and aquatic monocots. There is biotechnological interest in this enzyme group because apiose is the flavor-active compound of grapes, fruit juice, and wine, and the monosaccharide is found to be a plant secondary metabolite with pharmaceutical properties. However, functional and structural studies of this enzyme family are scarce. Recently, a glycoside hydrolase family member GH140 was isolated from Bacteroides thetaiotaomicron and identified as an endo-apiosidase.RESULTS: The structural characterization and functional identification of a second GH140 family enzyme, termed MmApi, discovered through mangrove soil metagenomic approach, are described. Among the various substrates tested, MmApi exhibited activity on an apiose-containing oligosaccharide derived from the pectic polysaccharide rhamnogalacturonan-II. While the crystallographic model of MmApi was similar to the endo-apiosidase from Bacteroides thetaiotaomicron, differences in the shape of the binding sites indicated that MmApi could cleave apioses within oligosaccharides of different compositions.CONCLUSION: This enzyme represents a novel tool for researchers interested in studying the physiology and structure of plant cell walls and developing biocatalytic strategies for drug and flavor production.</p

Heterologous expression and functional characterization of a GH10 endoxylanase from \u3ci\u3eAspergillus fumigatus\u3c/i\u3e var. \u3ci\u3eniveus\u3c/i\u3e with potential biotechnological application

Xylanases decrease the xylan content in pretreated biomass releasing it from hemicellulose, thus improving the accessibility of cellulose for cellulases. In this work, an endo-β-1,4-xylanase from Aspergillus fumigatus var. niveus (AFUMN-GH10) was successfully expressed. The structural analysis and biochemical characterization showed this AFUMN-GH10 does not contain a carbohydrate-binding module. The enzyme retained its activity in a pH range from 4.5 to 7.0, with an optimal temperature at 60°C. AFUMN-GH10 showed the highest activity in beechwood xylan. The mode of action of AFUMNGH10 was investigated by hydrolysis of APTS-labeled xylohexaose, which resulted in xylotriose and xylobiose as the main products. AFUMN-GH10 released 27% of residual xylan from hydrothermally-pretreated corn stover and 14% of residual xylan from hydrothermally-pretreated sugarcane bagasse. The results showed that environmentally friendly pretreatment followed by enzymatic hydrolysis with AFUMN-GH10 in low concentration is a suitable method to remove part of residual and recalcitrant hemicellulose from biomass