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1.
Nat Commun ; 12(1): 271, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431867

RESUMO

Dietary patterns and psychosocial factors, ubiquitous part of modern lifestyle, critically shape the gut microbiota and human health. However, it remains obscure how dietary and psychosocial inputs coordinately modulate the gut microbiota and host impact. Here, we show that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cells (ISC) renewal and epithelial homeostasis. Chow diet (CD) and purified diet (PD) confer distinct vulnerability to gut epithelial injury, microbial alternation and ISC dysfunction in chronically restrained mice. CD preferably enriches Lactobacillus reuteri, and its colonization is sufficient to rescue stress-triggered epithelial injury. Mechanistically, dietary raffinose sustains Lactobacillus reuteri growth, which in turn metabolizes raffinose to fructose and thereby constituting a feedforward metabolic loop favoring ISC maintenance during stress. Fructose augments and engages glycolysis to fuel ISC proliferation. Our data reveal a diet-stress interplay that dictates microbial metabolism-shaped ISC turnover and is exploitable for alleviating gut disorders.


Assuntos
Bactérias/metabolismo , Autorrenovação Celular , Dieta , Intestinos/microbiologia , Células-Tronco/citologia , Estresse Fisiológico , Animais , Metabolismo dos Carboidratos , Proliferação de Células , Doença Crônica , Células Epiteliais/microbiologia , Feminino , Frutose/metabolismo , Microbioma Gastrointestinal , Glicólise , Lactobacillus/metabolismo , Camundongos Endogâmicos BALB C , Polifenóis/metabolismo , Rafinose/metabolismo
2.
Nat Commun ; 11(1): 5436, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116123

RESUMO

Harmful effects of high fructose intake on health have been widely reported. Although fructose is known to promote cancer, little is known about the underlying mechanisms. Here, we found that fructose triggers breast cancer metastasis through the ketohexokinase-A signaling pathway. Molecular experiments showed that ketohexokinase-A, rather than ketohexokinase-C, is necessary and sufficient for fructose-induced cell invasion. Ketohexokinase-A-overexpressing breast cancer was found to be highly metastatic in fructose-fed mice. Mechanistically, cytoplasmic ketohexokinase-A enters into the nucleus during fructose stimulation, which is mediated by LRRC59 and KPNB1. In the nucleus, ketohexokinase-A phosphorylates YWHAH at Ser25 and the YWHAH recruits SLUG to the CDH1 promoter, which triggers cell migration. This study provides the effect of nutrition on breast cancer metastasis. High intake of fructose should be restricted in cancer patients to reduce the risk of metastasis. From a therapeutic perspective, the ketohexokinase-A signaling pathway could be a potential target to prevent cancer metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Frutoquinases/metabolismo , Frutose/administração & dosagem , Frutose/metabolismo , Proteínas 14-3-3/antagonistas & inibidores , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Animais , Carcinógenos/administração & dosagem , Carcinógenos/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Fosforilação , Transdução de Sinais , beta Carioferinas/metabolismo
3.
Mol Genet Genomics ; 295(6): 1489-1500, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32948893

RESUMO

Glucose, fructose and mannose are the preferred carbon/energy sources for the yeast Saccharomyces cerevisiae. Absence of preferred energy sources activates glucose derepression, which is regulated by the kinase Snf1. Snf1 phosphorylates the transcriptional repressor Mig1, which results in its exit from the nucleus and subsequent derepression of genes. In contrast, Snf1 is inactive when preferred carbon sources are available, which leads to dephosphorylation of Mig1 and its translocation to the nucleus where Mig1 acts as a transcription repressor. Here we revisit the role of the three hexose kinases, Hxk1, Hxk2 and Glk1, in glucose de/repression. We demonstrate that all three sugar kinases initially affect Mig1 nuclear localization upon addition of glucose, fructose and mannose. This initial import of Mig1 into the nucleus was temporary; for continuous nucleocytoplasmic shuttling of Mig1, Hxk2 is required in the presence of glucose and mannose and in the presence of fructose Hxk2 or Hxk1 is required. Our data suggest that Mig1 import following exposure to preferred energy sources is controlled via two different pathways, where (1) the initial import is regulated by signals derived from metabolism and (2) continuous shuttling is regulated by the Hxk2 and Hxk1 proteins. Mig1 nucleocytoplasmic shuttling appears to be important for the maintenance of the repressed state in which Hxk1/2 seems to play an essential role.


Assuntos
Núcleo Celular/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Hexoquinase/metabolismo , Manose/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transporte Ativo do Núcleo Celular , Regulação Fúngica da Expressão Gênica , Hexoquinase/genética , Fosforilação , Transporte Proteico , Proteínas Repressoras/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética
4.
PLoS One ; 15(6): e0235415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598354

RESUMO

To better understand the mechanism of inherent salt resistance in Jerusalem artichoke (Helianthus tuberosus L.), physiological and metabolic responses of tubers at the initiation stage of sprouting under different salt stress levels were evaluated in the present study. As a result, 28 metabolites were identified using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Jerusalem artichoke tubers showed minor changes in metabolic response under moderate salt stress when they had not yet sprouted, where metabolism was downregulated at the start of sprouting and then upregulated significantly after plants became autotrophic. However, mild and severe salt stress levels caused different metabolic response patterns. In addition, the accumulation of fructose and sucrose was enhanced by moderate salt stress, while glucose was highly consumed. Aspartate and asparagine showed accelerated accumulation in sprouting Jerusalem artichoke tubers that became autotrophic, suggesting the enhancement of photosynthesis by moderate salt stress.


Assuntos
Frutose/metabolismo , Glucose/metabolismo , Helianthus/metabolismo , Tubérculos/metabolismo , Estresse Salino , Sacarose/metabolismo , Helianthus/crescimento & desenvolvimento , Fotossíntese , Tubérculos/crescimento & desenvolvimento
5.
PLoS One ; 15(5): e0233779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470059

RESUMO

Trehalose metabolism in yeast has been linked to a variety of phenotypes, including heat resistance, desiccation tolerance, carbon-source utilization, and sporulation. The relationships among the several phenotypes of mutants unable to synthesize trehalose are not understood, even though the pathway is highly conserved. One of these phenotypes is that tps1Δ strains cannot reportedly grow on media containing glucose or fructose, even when another carbon source they can use (e.g. galactose) is present. Here we corroborate the recent observation that a small fraction of yeast tps1Δ cells do grow on glucose, unlike the majority of the population. This is not due to a genetic alteration, but instead resembles the persister phenotype documented in many microorganisms and cancer cells undergoing lethal stress. We extend these observations to show that this phenomenon is glucose-specific, as it does not occur on another highly fermented carbon source, fructose. We further demonstrate that this phenomenon appears to be related to mitochondrial complex III function, but unrelated to inorganic phosphate levels in the cell, as had previously been suggested. Finally, we found that this phenomenon is specific to S288C-derived strains, and is the consequence of a variant in the MKT1 gene.


Assuntos
Glucose/metabolismo , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Fermentação , Frutose/metabolismo , Glucosiltransferases/genética , Mutação com Perda de Função , Trealose/biossíntese
6.
PLoS One ; 15(5): e0233285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453779

RESUMO

Fermentation by microorganisms is a key step in the production of traditional food products such as bread, cheese, beer and wine. In these fermentative ecosystems, microorganisms interact in various ways, namely competition, predation, commensalism and mutualism. Traditional wine fermentation is a complex microbial process performed by Saccharomyces and non-Saccharomyces (NS) yeast species. To better understand the different interactions occurring within wine fermentation, isolated yeast cultures were compared with mixed co-cultures of one reference strain of S. cerevisiae with one strain of four NS yeast species (Metschnikowia pulcherrima, M. fructicola, Hanseniaspora opuntiae and H. uvarum). In each case, we studied population dynamics, resource consumed and metabolites produced from central carbon metabolism. This phenotyping of competition kinetics allowed us to confirm the main mechanisms of interaction between strains of four NS species. S. cerevisiae competed with H. uvarum and H. opuntiae for resources although both Hanseniaspora species were characterized by a strong mortality either in mono or mixed fermentations. M. pulcherrima and M. fructicola displayed a negative interaction with the S. cerevisiae strain tested, with a decrease in viability in co-culture. Overall, this work highlights the importance of measuring specific cell populations in mixed cultures and their metabolite kinetics to understand yeast-yeast interactions. These results are a first step towards ecological engineering and the rational design of optimal multi-species starter consortia using modeling tools. In particular the originality of this paper is for the first times to highlight the joint-effect of different species population dynamics on glycerol production and also to discuss on the putative role of lipid uptake on the limitation of some non-conventional species growth although interaction processes.


Assuntos
Fermentação , Hanseniaspora/metabolismo , Metschnikowia/metabolismo , Saccharomyces cerevisiae/metabolismo , Vinho/microbiologia , Dióxido de Carbono/metabolismo , Fermentação/fisiologia , Frutose/metabolismo , Sucos de Frutas e Vegetais/microbiologia , Glucose/metabolismo , Cinética , Nitrogênio/metabolismo , Vitis
7.
Food Microbiol ; 90: 103464, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32336355

RESUMO

Achieving a high monosaccharide composition in malt wort is instrumental to achieve successful lactic acid bacteria fermentation of malt based beverages. The conversion of monosaccharides to alternative metabolites such as the sweet polyol, mannitol with heterofermentative strains presents a novel approach for sugar reduction and to compensate for the loss of sweetness. This work outlines the application of an adopted mashing regimen with the addition of exogenous enzymes to produce wort with high fructose content which can be applied to different malted grain types with consistently efficacious monosaccharide production for bacterial fermentation. The so produced worts are then fermented with Leuconostoc citreum TR116 a mannitol hyper-producer. Malted barley, oat and wheat were mashed to stimulate protein degradation and release of free amino acids along with the enzymatic conversion of starch to fermentable sugars. Amyloglucosidase and glucose isomerase treatment converted di- and oligo-saccharides to glucose and provided a moderate fructose concentration in malt worts which was consistent across the three cereals. Fructose was completely depleted during fermentation with Lc. Citreum TR116 and converted to mannitol with high efficiency (>90%) while overall sugar reduction was >25% in all malt worts. Differences in amino acid composition of malt worts did not significantly affect growth of Lc. Citreum TR116 but did affect the formation of the aroma compounds diacetyl and isoamyl alcohol. Organic acid production and acidification of wort was similar across cereal substrates and acetic acid formation was linked to yield of mannitol. The results suggest that differences in amino acid and fructose content of malt worts considerably change metabolite formation during fermentation with Lc. Citreum TR116, a mannitol hyper-producer. This work gives new insight into the development of consumer acceptable malt based beverages which will provide further options for the health conscious and diabetic consumer, an important step in the age of sugar overconsumption.


Assuntos
Grão Comestível/microbiologia , Fermentação , Alimentos e Bebidas Fermentados/microbiologia , Leuconostoc/metabolismo , Manitol/metabolismo , Açúcares/metabolismo , Avena/química , Avena/microbiologia , Reatores Biológicos , Frutose/metabolismo , Hordeum/química , Hordeum/microbiologia , Lactobacillales/metabolismo , Leuconostoc/crescimento & desenvolvimento , Triticum/química , Triticum/microbiologia
8.
Comp Biochem Physiol B Biochem Mol Biol ; 243-244: 110437, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32247057

RESUMO

Salinity is an important abiotic factor for aquatic organisms. In fish, changes in salinity affect physiological responses and alter the immune system. Takifugu rubripes is an important economic marine fish, and mechanisms of T. rubripes adaptation to salinity changes need to be further documented. In this study, a transcriptome sequencing technique was used to analyse genes that were differentially expressed in the T. rubripes gill after low-salinity stress for 30 d, and differential gene expression was further validated by quantitative real-time PCR (qPCR). After assembly, 385 differentially expressed genes (DEGs) were identified, including 182 upregulated genes and 203 downregulated genes. The DEGs were assigned to Gene Ontology (GO) classes with a total of 1647 functional terms. Most DEGs were assigned to biological process (984; 59.8%) followed by molecular function (445; 27.0%) and cellular component (218; 13.2%). Further KEGG analysis allocated 385 DEGs to 95 KEGG pathways. After q-value correction, 7 pathways (Glycolysis/Gluconeogenesis; Biosynthesis of amino acids; Carbon metabolism; Fructose and mannose metabolism; Pentose phosphate pathway; Metabolism of xenobiotics by cytochrome P450; and Glycine, serine and threonine metabolism) remained significant. qPCR results indicated that the transcripts of six selected genes sharply increased after 30 d of low-salinity stress. Low-salinity stress obviously increased SLC39A6, SLC5A9, NKAα1, CYP1A1, CYP1B1, and GSTA expression. In contrast, the genes encoding Aldoaa, GPI, FBP2 and GAPDH exhibited downregulation. In addition, three solute carrier (SLC) genes selected from the DEGs were further studied for differential expression patterns after low-salinity exposure, and the results showed that the SLCs were upregulated in T. rubripes after 72 h of low-salinity exposure. This investigation provides data for understanding the molecular mechanisms of fish responses to low-salinity stress and provides a reference for rationally setting salinity levels in aquaculture.


Assuntos
Estresse Salino/genética , Transdução de Sinais/genética , Takifugu/metabolismo , Transcriptoma/genética , Aclimatação/genética , Aminoácidos/metabolismo , Animais , Frutose/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Ontologia Genética , Gluconeogênese/genética , Glicólise/genética , Manose/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Takifugu/genética
9.
Enzyme Microb Technol ; 136: 109531, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32331724

RESUMO

d-Psicose, as important rare sugar and epimer of d-fructose on the C-3 position, displays unique health benefits and physiological functions in various fields. The production of d-psicose is currently obtained via enzymatic bioconversion, mostly with of d-tagatose 3-epimerase. In the present study, the isomerization of d-fructose into d-psicose was achieved by constructing engineered food-grade Bacillus subtilis through fermentation. After optimizing the fermentation conditions of the recombinant strain, the yield of d-psicose reached up to 4.56 g/L, representing an over 8-fold increase in the yield compared to unoptimized conditions, with a d-fructose conversion rate of 56.26 % when the strain was cultured at 35 ℃ for 24 h with 5 g/L d-fructose and 5 mM of Mn2+. In addition, 30 g of wasted apple hydrolysate were fermented by engineered B. subtilis and gained 7.76 g/L of d-psicose at a conversion rate of 25.86 % (w/w).


Assuntos
Bacillus subtilis/genética , Carboidratos Epimerases/genética , Carboidratos Epimerases/metabolismo , Fermentação , Frutose/metabolismo , Biocatálise , Clonagem Molecular , Hexoses , Concentração de Íons de Hidrogênio , Microbiologia Industrial , Cinética , Especificidade por Substrato , Temperatura
10.
Plant Mol Biol ; 103(4-5): 511-525, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279151

RESUMO

KEY MESSAGE: TPST is involved in fructose signaling to regulate the root development and expression of genes in biological processes including auxin biosynthesis and accumulation in Arabidopsis. Sulfonation of proteins by tyrosine protein sulfotransferases (TPST) has been implicated in many important biological processes in eukaryotic organisms. Arabidopsis possesses a single TPST gene and its role in auxin homeostasis and root development has been reported. Here we show that the Arabidopsis tpst mutants are hypersensitive to fructose. In contrast to sucrose and glucose, fructose represses primary root growth of various ecotypes of Arabidopsis at low concentrations. RNA-seq analysis identified 636 differentially expressed genes (DEGs) in Col-0 seedlings in response to fructose verses glucose. GO and KEGG analyses of the DEGs revealed that fructose down-regulates genes involved in photosynthesis, glucosinolate biosynthesis and IAA biosynthesis, but up-regulates genes involved in the degradation of branched amino acids, sucrose starvation response, and dark response. The fructose responsive DEGs in the tpst mutant largely overlapped with that in Col-0, and most DEGs in tpst displayed larger changes than in Col-0. Interestingly, the fructose up-regulated DEGs includes genes encoding two AtTPST substrate proteins, Phytosulfokine 2 (PSK2) and Root Meristem Growth Factor 7 (RGF7). Synthesized peptides of PSK-α and RGF7 could restore the fructose hypersensitivity of tpst mutant plants. Furthermore, auxin distribution and accumulation at the root tip were affected by fructose and the tpst mutation. Our findings suggest that fructose serves as a signal to regulate the expression of genes involved in various biological processes including auxin biosynthesis and accumulation, and that modulation of auxin accumulation and distribution in roots by fructose might be partly mediated by the TPST substrate genes PSK-α and RGF7.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Frutose/metabolismo , Raízes de Plantas/metabolismo , Sulfotransferases/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Glucose/metabolismo , Ácidos Indolacéticos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Meristema/metabolismo , Hormônios Peptídicos/genética , Hormônios Peptídicos/metabolismo , Proteínas de Plantas , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Plântula/crescimento & desenvolvimento , Transdução de Sinais , Sulfotransferases/genética , Transcriptoma
11.
J Biosci Bioeng ; 130(1): 36-47, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32179024

RESUMO

Ansamitocin P-3 (AP-3) shows strong anticancer effects and has used as a payload for antibody-drug conjugates. Our previous study have shown that although genetically engineered Actinosynnema pretiosum strains with enhanced UDP-glucose (UDPG) biosynthesis displayed improved AP-3 production compared to the wild-type strain, the increase in yield was far from meeting the industrial demand. In this study, comparative metabolomics analysis complemented with quantitative real-time PCR analysis was performed for the wild-type strain and two mutants (OpgmOugp, ΔzwfΔgnd) to identify possible metabolic bottlenecks and non-intuitive targets for further enhancement of AP-3 production. We observed that enhancing intracellular UDPG availability facilitated the accumulation of intracellular N-demethyl-AP-3 and AP-3, where the transporting of them outside the cell still needs to be developed. We also found that the UDPG biosynthesis was closely associated with the availability of fructose in the medium and a suitable fructose feeding strategy could promote the further improvement of AP-3 titer. In addition, pathway abundance analysis revealed that undesired fatty acid accumulation and down-regulation of amino acid metabolism may be unfavorable for ansamitocin biosynthesis in later stage of production. These results indicate that genetic modification of the UDPG biosynthetic pathways may have pleiotropic effects on AP-3 production. Efforts must be made to eliminate these newly identified metabolic bottlenecks to boost AP-3 production in A. pretiosum.


Assuntos
Actinobacteria/metabolismo , Maitansina/análogos & derivados , Uridina Difosfato Glucose/metabolismo , Actinobacteria/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Vias Biossintéticas/genética , Frutose/metabolismo , Maitansina/biossíntese , Metabolômica
12.
Nature ; 579(7800): 586-591, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214246

RESUMO

Consumption of fructose has risen markedly in recent decades owing to the use of sucrose and high-fructose corn syrup in beverages and processed foods1, and this has contributed to increasing rates of obesity and non-alcoholic fatty liver disease2-4. Fructose intake triggers de novo lipogenesis in the liver4-6, in which carbon precursors of acetyl-CoA are converted into fatty acids. The ATP citrate lyase (ACLY) enzyme cleaves cytosolic citrate to generate acetyl-CoA, and is upregulated after consumption of carbohydrates7. Clinical trials are currently pursuing the inhibition of ACLY as a treatment for metabolic diseases8. However, the route from dietary fructose to hepatic acetyl-CoA and lipids remains unknown. Here, using in vivo isotope tracing, we show that liver-specific deletion of Acly in mice is unable to suppress fructose-induced lipogenesis. Dietary fructose is converted to acetate by the gut microbiota9, and this supplies lipogenic acetyl-CoA independently of ACLY10. Depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis. By contrast, the lipogenic transcriptional program is activated in response to fructose in a manner that is independent of acetyl-CoA metabolism. These data reveal a two-pronged mechanism that regulates hepatic lipogenesis, in which fructolysis within hepatocytes provides a signal to promote the expression of lipogenic genes, and the generation of microbial acetate feeds lipogenic pools of acetyl-CoA.


Assuntos
Acetatos/metabolismo , Açúcares da Dieta/metabolismo , Frutose/metabolismo , Microbioma Gastrointestinal/fisiologia , Lipogênese , Fígado/metabolismo , ATP Citrato (pro-S)-Liase/deficiência , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Acetato-CoA Ligase/deficiência , Acetato-CoA Ligase/genética , Acetato-CoA Ligase/metabolismo , Acetilcoenzima A/metabolismo , Animais , Ácido Cítrico/metabolismo , Açúcares da Dieta/administração & dosagem , Açúcares da Dieta/farmacologia , Ácidos Graxos/metabolismo , Frutose/administração & dosagem , Frutose/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Marcação por Isótopo , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Especificidade por Substrato
13.
Nature ; 579(7800): 507-517, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214253

RESUMO

Tumours depend on nutrients supplied by the host for their growth and survival. Modifications to the host's diet can change nutrient availability in the tumour microenvironment, which might represent a promising strategy for inhibiting tumour growth. Dietary modifications can limit tumour-specific nutritional requirements, alter certain nutrients that target the metabolic vulnerabilities of the tumour, or enhance the cytotoxicity of anti-cancer drugs. Recent reports have suggested that modification of several nutrients in the diet can alter the efficacy of cancer therapies, and some of the newest developments in this quickly expanding field are reviewed here. The results discussed indicate that the dietary habits and nutritional state of a patient must be taken into account during cancer research and therapy.


Assuntos
Dieta , Neoplasias/dietoterapia , Neoplasias/terapia , Estado Nutricional , Aminoácidos/deficiência , Aminoácidos/metabolismo , Animais , Suplementos Nutricionais , Jejum/fisiologia , Ácidos Graxos/metabolismo , Ácido Fólico/metabolismo , Frutose/deficiência , Frutose/metabolismo , Glucose/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia
14.
Enzyme Microb Technol ; 135: 109494, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146933

RESUMO

Glucose isomerase (GIase), an efficient enzyme in the isomerization of d-glucose to d-fructose, has been widely used in food processing. In this study, an efficient expression system for a Thermobifida fusca GIase (GIaseTfus) in Escherichia coli was firstly designed via a two-stage feeding strategy for improving expression level. The cultivation strategy was performed at an exponential feeding rate during the pre-induction phase, followed by a gradient-decreasing feeding rate at the induction phase in a 3-L fermenter. During this process, the effect of induction conditions and the complex nitrogen supplementation in feeding solutions on GIaseTfus production were investigated and optimized. Under the optimal conditions, the yield of GIaseTfus reached 124.1 U/mL, which is the highest expression level of GIase by recombinant E. coli reported to date. Additionally, the obtained GIaseTfus was performed to produce high fructose corn syrup (HFCS) with conversion approacing 55 % from glucose (45 %, w/v) to fructose. According to the molecular dynamic simulation, a number of hydrogen bonds existed in the enzyme-substrate complex could stablilize the transient states, and a appreciate reaction distance of M1 catalytic site and oxygen atom of glucose make the reaction proceed easily, thus resulting in the efficient biosynthesis of HFCS. The function of GIaseTfus renders it a valuable catalyst for HFCS-55 (containing 55 % d-fructose) manufacturing, the most favorable industrial product of HFCS. The efficient expression of GIaseTfus and its efficient HFCS production lays the foundation for its proming industrial application.


Assuntos
Actinobacteria/enzimologia , Aldose-Cetose Isomerases/metabolismo , Proteínas de Bactérias/metabolismo , Xarope de Milho Rico em Frutose/metabolismo , Actinobacteria/genética , Aldose-Cetose Isomerases/química , Aldose-Cetose Isomerases/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Domínio Catalítico , Escherichia coli/genética , Escherichia coli/metabolismo , Frutose/metabolismo , Expressão Gênica , Glucose/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
15.
Lett Appl Microbiol ; 70(4): 331-339, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32003005

RESUMO

The fructophilic bacterium Fructobacillus fructosus MCC 3996 described in the present investigation was isolated from the nectar of Butea monosperma flower and evaluated in vitro for the manifestation of probiotic features. The strain utilizes fructose faster than glucose and is capable to grow in the range of 1-35% fructose concentration (optimum 5% w/v) and thus denotes its fructophilic nature. In vitro assessments of the strain have examined for the endurance in acidic environment/gastric juice, the better auto-aggregation ability even in the presence of hydrolytic enzymes, co-aggregation with pathogenic bacteria, hydrophobicity properties and no haemolytic activity to elucidate its feasible probiotic use. The significant antagonistic activity against several detrimental bacteria, despite lacking the bacteriocin secretion, is an astonishing feature. Owing to the indigenous origin of the isolate, it could be used as a probiotic, starter culture, and/or the active ingredient of food formulation may contribute to improve the desirable fermentation, long-term storage and nutritional benefits of foods especially rich in fructose. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided in vitro evidence that Fructobacillus fructosus MCC 3996 have endurance in acidic gastric juice, better co-aggregation, auto-aggregation properties, splendid antagonistic activities against several bacteria involved in food spoilage/human infections, pertinent antibiotic susceptibility profile and no haemolytic activity. Also, F. fructosus have the capability to survive in the appreciable amount of fructose, and this advocates that the strain could be used as starter culture and/or the active ingredient of fructose-rich foods. The current in vitro study provided a strong basis for further in vivo research to identify the health beneficial characteristics of F. fructosus and its potential could be effectively utilized as health-boosting ingredient in food and pharmaceutical industries.


Assuntos
Butea/microbiologia , Leuconostocaceae/isolamento & purificação , Fermentação , Flores/microbiologia , Frutose/metabolismo , Glucose/metabolismo , Leuconostocaceae/classificação , Leuconostocaceae/genética , Leuconostocaceae/metabolismo , Filogenia , Probióticos/análise , Probióticos/classificação , Probióticos/metabolismo
16.
Food Chem ; 315: 126265, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32014668

RESUMO

Protein glycation plays a vital role in the progression of various diabetes complications. Therefore, inhibition of protein glycation could be a key strategy to prevent these diabetic abnormalities. Evaluation of phenolic compositions and their antiglycation activity revealed that p-coumaric and chlorogenic acids were major phenolic acids in barnyard millet. These phenolics exhibited multiple antioxidant activities in various mechanisms and protected the oxidative DNA damage and hydroxyl radical-induced protein fragmentation. Millet phenolics were very effective in scavenging >78% reactive carbonyl intermediates in the reaction and protected protein thiol group oxidation. Furthermore, 68.3% inhibition of protein glycation and reduced formation of protein aggregates were also observed with millet phenolics. Besides, fluorescence intensity measurements indicated a significant decrease in advance glycated end products and protection against glycoxidation-induced protein conformational changes at 100 µg/ml phenolics. These results suggest the potential utility of barnyard millet as an ingredient in functional foods for controlling protein glycation associated diabetic complications.


Assuntos
Echinochloa/química , Produtos Finais de Glicação Avançada/metabolismo , Fenóis/farmacologia , Proteínas/metabolismo , Antioxidantes/análise , Antioxidantes/farmacologia , Frutose/metabolismo , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Oxirredução , Fenóis/análise , Fenóis/isolamento & purificação , Extratos Vegetais/química , Proteínas/química , Soroalbumina Bovina/metabolismo
17.
Int J Food Microbiol ; 321: 108546, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32087410

RESUMO

The demand for sugar reduction in products across the food and beverage industries has evoked the development of novel processes including the application of fermentation with lactic acid bacteria. Heterofermentative lactic acid bacteria (LAB) are diverse in their ability to utilise fermentable sugars and can also convert fructose into the sweet tasting polyol, mannitol. The sourdough microbiota has long been recognised as an ecological niche for a range of homofermentative and heterofermentative lactic acid bacteria. A leading determinant in the biodiversity of sourdough microbial populations is the type of flour used. Ten non-wheat flours were used and back-slopped for 7 days resulting in the isolation of 52 mannitol producing isolates which spanned six heterofermentative species of the genera Lactobacillus, Leuconostoc and Weissella. Assessment of mannitol productivity in fructose concentrations up to 100 g/L found Leuconostoc citreum TR116, to have the best mannitol producing characteristics, consuming 95% of available fructose and yielding 0.68 g of mannitol per gram of fructose consumed which equates to the maximal theoretical yield. Investigation of the effects of initial pH on mannitol production and other fermentation parameters in the isolates found pH 7 to be best for isolates Lactobacillus brevis TR052, Leuconostoc fallax TR111, Leuconostoc citreum TR116, Leuconostoc mesenteroides TR154 and Weissella paramesenteroides TR212, while pH 6 was optimal for Leuconostoc pseudomesenteroides TR080. The fermentation of apple juice with each isolate resulted in sugar reduction ranging from 30.3-74.0 g/L (34-72%). When apple juice fermentation with Leuconostoc citreum TR116 was scaled up to 1 L bioreactor a reduction in sugar of 98.6 g/L (83%) was achieved along with the production of 61.6 g/L mannitol. This demonstrates a fermentative process for sugar reduction in fruit juice with concomitant production of the sweet metabolite mannitol to create a fermentate that is suitable for further development as a low sugar fruit juice alternative.


Assuntos
Lactobacillales/isolamento & purificação , Lactobacillales/metabolismo , Manitol/metabolismo , Açúcares/metabolismo , Biodiversidade , Reatores Biológicos/microbiologia , Pão/microbiologia , Fermentação , Microbiologia de Alimentos , Frutose/metabolismo , Concentração de Íons de Hidrogênio , Lactobacillales/classificação
18.
Microb Cell Fact ; 19(1): 39, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070345

RESUMO

The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of L-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. L-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTSGlc and PTSFru) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and L-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L L-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of L-lysine production from mixed sugar. This is also the first report for improving the efficiency of L-lysine production by systematic modification of carbohydrate metabolism systems.


Assuntos
Corynebacterium glutamicum/metabolismo , Frutose/metabolismo , Lisina/biossíntese , Engenharia Metabólica , Sacarose/metabolismo , Proteínas de Bactérias/metabolismo , Corynebacterium glutamicum/crescimento & desenvolvimento , Fermentação
19.
J Virol ; 94(9)2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32102878

RESUMO

Semen is the primary transmission vehicle for various pathogenic viruses. Initial steps of transmission, including cell attachment and entry, likely occur in the presence of semen. However, the unstable nature of human seminal plasma and its toxic effects on cells in culture limit the ability to study in vitro virus infection and inhibition in this medium. We found that whole semen significantly reduces the potency of antibodies and microbicides that target glycans on the envelope glycoproteins (Envs) of HIV-1. The extraordinarily high concentration of the monosaccharide fructose in semen contributes significantly to the effect by competitively inhibiting the binding of ligands to α1,2-linked mannose residues on Env. Infection and inhibition in whole human seminal plasma are accurately mimicked by a stable synthetic simulant of seminal fluid that we formulated. Our findings indicate that, in addition to the protein content of biological secretions, their small-solute composition impacts the potency of antiviral microbicides and mucosal antibodies.IMPORTANCE Biological secretions allow viruses to spread between individuals. Each type of secretion has a unique composition of proteins, salts, and sugars, which can affect the infectivity potential of the virus and inhibition of this process. Here, we describe HIV-1 infection and inhibition in whole human seminal plasma and a synthetic simulant that we formulated. We discovered that the sugar fructose in semen decreases the activity of a broad and potent class of antiviral agents that target mannose sugars on the envelope protein of HIV-1. This effect of semen fructose likely reduces the efficacy of such inhibitors to prevent the sexual transmission of HIV-1. Our findings suggest that the preclinical evaluation of microbicides and vaccine-elicited antibodies will be improved by their in vitro assessment in synthetic formulations that simulate the effects of semen on HIV-1 infection and inhibition.


Assuntos
Frutose/metabolismo , Frutose/farmacologia , Sêmen/metabolismo , Adulto , Anti-Infecciosos/farmacologia , Antivirais/antagonistas & inibidores , Antivirais/farmacologia , Linhagem Celular Tumoral , Produtos do Gene env/metabolismo , Genes env/genética , Células HEK293 , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Masculino , Manose/metabolismo , Polissacarídeos/imunologia , Polissacarídeos/metabolismo , Sêmen/virologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
20.
J Agric Food Chem ; 68(5): 1436-1446, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927917

RESUMO

High fructose intake promotes hepatic lipid accumulation. Pterostilbene, a natural analogue of resveratrol found in diet berries, exhibits a hepatoprotective property. Here, we studied the protection by pterostilbene against fructose-induced hepatic lipid accumulation and explored its possible mechanism. We observed a high expression of microRNA-34a (miR-34a, P < 0.05) and a low expression of its target, sirtuin1 (Sirt1, mRNA: P < 0.01; protein: P < 0.001), with the overactivation of downstream sterol regulatory element-binding protein-1 (SREBP-1) lipogenic pathway (nuclear SREBP-1 protein: P < 0.05; FAS and SCD1 mRNA: P < 0.01), in rat livers, as well as BRL-3A and HepG2 cells, stimulated by fructose. More interestingly, pterostilbene recovered the fructose-disturbed miR-34a expression (0.3-0.5-fold vs fructose control, P < 0.05), Sirt1 protein level (1.2- to 1.5-fold vs fructose control, P < 0.05), and SREBP-1 lipogenic pathway, resulting in significant amelioration of hepatocyte lipid accumulation in animal [hepatic triglyceride and total cholesterol (TG&TC) mg/g·wet tissue: 4.90 ± 0.19, 5.23 ± 0.16, 5.20 ± 0.29 vs fructose control 9.73 ± 1.06, P < 0.001; 3.18 ± 0.30, 3.31 ± 0.39, 3.37 ± 0.47 vs 5.67 ± 0.28, P < 0.001] and cell models (BRL-3A TG&TC mmol/g·protein: 0.123 ± 0.011 vs 0.177 ± 0.004, P < 0.001; 0.169 ± 0.011 vs 0.202 ± 0.008, P < 0.05; HepG2: 0.257 ± 0.005 vs 0.303 ± 0.016, P < 0.05; 0.143 ± 0.004 vs 0.201 ± 0.008, P < 0.001). These results provide the experimental evidence supporting the anti-lipogenic effect of pterostilbene against fructose-induced hepatic lipid accumulation via modulating the miR-34a/Sirt1/SREBP-1 pathway.


Assuntos
Frutose/metabolismo , Fígado/efeitos dos fármacos , MicroRNAs/metabolismo , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Estilbenos/administração & dosagem , Animais , Colesterol/metabolismo , Frutose/efeitos adversos , Fígado/metabolismo , Masculino , MicroRNAs/genética , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Triglicerídeos/metabolismo
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