Plant metabolomics and metabolic biology

<正>Plants produce a large array of specialized metabolites(natural products)that not only are essential for growth and development,but also play important roles in adaptation to the variable stressful environments.Also,many plant metabolites are essential nutrient elements for humans and serve as natural drugs.However,study of the biosynthesis of natural products is still in its infancy,because more than 90%of plant     

A new metabolomics analysis technique: steady-state metabolic network dynamics analysis

With the recent advances in experimental technologies, such as gas chromatography and mass spectrometry, the number of metabolites that can be measured in biofluids of individuals has markedly increased. Given a set of such measurements, a very common task encountered by biologists is to identify the metabolic mechanisms that lead to changes in the concentrations of given metabolites and interpret the metabolic consequences of the observed changes in terms of physiological problems, nutritional deficiencies, or diseases. In this paper, we present the steady-state metabolic network dynamics analysis (SMDA) approach in detail, together with its application in a cystic fibrosis study. We also present a computational performance evaluation of the SMDA tool against a mammalian metabolic network database. The query output space of the SMDA tool is exponentially large in the number of reactions of the network. However, (i) larger numbers of observations exponentially reduce the output size, and (ii) exploratory search and browsing of the query output space is provided to allow users to search for what they are looking for.     

Integrating genomics and metabolomics for engineering plant metabolic pathways

Plant metabolites are characterized by an enormous chemical diversity, every plant having its own complex set of metabolites. This variety poses analytical challenges, both for profiling multiple metabolites in parallel and for the quantitative analysis of selected metabolites. We are only just starting to understand the roles of these metabolites, many of them being involved in adaptations to specific ecological niches and some finding beneficial use (e.g. as pharmaceuticals). Spectacular advances in plant metabolomics offer new possibilities, together with the aid of systems biology, to explore the extraordinary complexity of the plant biochemical capacity. State-of-the art genomics tools can be combined with metabolic profiling to identify key genes that could be engineered for the production of improved crop plants.     

Flux analysis and metabolomics for systematic metabolic engineering of microorganisms

Rational engineering of metabolism is important for bio-production using microorganisms. Metabolic design based on in silico simulations and experimental validation of the metabolic state in the engineered strain helps in accomplishing systematic metabolic engineering. Flux balance analysis (FBA) is a method for the prediction of metabolic phenotype, and many applications have been developed using FBA to design metabolic networks. Elementary mode analysis (EMA) and ensemble modeling techniques are also useful tools for in silico strain design. The metabolome and flux distribution of the metabolic pathways enable us to evaluate the metabolic state and provide useful clues to improve target productivity. Here, we reviewed several computational applications for metabolic engineering by using genome-scale metabolic models of microorganisms. We also discussed the recent progress made in the field of metabolomics and ¹³C-metabolic flux analysis techniques, and reviewed these applications pertaining to bio-production development. Because these in silico or experimental approaches have their respective advantages and disadvantages, the combined usage of these methods is complementary and effective for metabolic engineering.     

Plant metabolomics reveals conserved and divergent metabolic responses to salinity

New metabolic profiling technologies provide data on a wider range of metabolites than traditional targeted approaches. Metabolomic technologies currently facilitate acquisition of multivariate metabolic data using diverse, mostly hyphenated, chromatographic detection systems, such as GC-MS or liquid chromatography coupled to mass spectrometry, Fourier-transformed infrared spectroscopy or NMR-based methods. Analysis of the resulting data can be performed through a combination of non-supervised and supervised statistical methods, such as independent component analysis and analysis of variance, respectively. These methods reduce the complex data sets to information, which is relevant for the discovery of metabolic markers or for hypothesis-driven, pathway-based analysis. Plant responses to salinity involve changes in the activity of genes and proteins, which invariably lead to changes in plant metabolism. Here, we highlight a selection of recent publications in the salt stress field, and use gas chromatography time-of-flight mass spectrometry profiles of polar fractions from the plant models, Arabidopsis thaliana, Lotus japonicus and Oryza sativa to demonstrate the power of metabolite profiling. We present evidence for conserved and divergent metabolic responses among these three species and conclude that a change in the balance between amino acids and organic acids may be a conserved metabolic response of plants to salt stress.     

Extracellular metabolomics: a metabolic footprinting approach to assess fiber degradation in complex media

This work reports the implementation and optimization of a method for high-throughput analysis of metabolites produced by the breakdown of natural polysaccharides by microorganisms. Our simple protocol enables simultaneous separation and quantification of more than 40 different sugars and sugar derivatives, in addition to several organic acids in complex media, using 50-mul samples and a standard gas chromatography-mass spectrometry platform that was fully optimized for this purpose. As an implementation proof-of-concept, we assayed extracellular metabolite levels of three bacterial strains cultivated on complex medium rich in polysaccharides and under identical growth conditions. We demonstrate that the metabolic footprinting profile data distinguish among sample types such as typical metabolomics data. Moreover, we demonstrate that the differential metabolite-level data provide insight on specific fibrolytic activity of the different microbial strains and lay the groundwork for integrated proteome-metabolome studies of fiber-degrading microorganisms.     

Proteomics and metabolomics in biomarker discovery for cardiovascular diseases: progress and potential

Introduction: The process of discovering novel biomarkers and potential therapeutic targets may be shortened using proteomic and metabolomic approaches.

Areas covered: Several complementary strategies, each one presenting different advantages and limitations, may be used with these novel approaches. In vitro studies show how cells involved in cardiovascular disease react, although the phenotype of cultured cells differs to that occurring in vivo. Tissue analysis either in human specimens or animal models may show the proteins that are expressed in the pathological process, although the presence of structural proteins may be confounding. To identify circulating biomarkers, analyzing the secretome of cultured atherosclerotic tissue, analysis of blood cells and/or plasma may be more straightforward. However, in the latter approach, high-abundant proteins may mask small molecules that could be potential biomarkers. The study of sub-proteomes such as high-density lipoproteins may be useful to circumvent this limitation. Regarding metabolomics, most studies have been performed in small populations, and we need to perform studies in large populations in order to discover robust biomarkers.

Expert commentary: It is necessary to involve the clinicians in these areas to improve the design of clinical studies, including larger populations, in order to obtain consistent novel biomarkers.     

Acute nephrotoxicity of aristolochic acid in vitro: metabolomics study for intracellular metabolic time-course changes

Time-course metabolic changes of aristolochic acid nephrotoxicity (AAN) was investigated using acute AAN HK-2 model. And the AAN-related biomarkers were selected. In the results, 11 potential identified biomarkers were selected and validated using multivariate method combined with time-course analysis. Several metabolic pathways, including vitamin metabolism, lipids acalytion, trytophan metabolism and protein degradation were found to be associated with AAN pathology. This research will provide a valuable reference for the discovery of more potential biomarkers of AAN progression in clinic.     

Antibodies in metabolic diseases

In the past century, incidences of chronic metabolic diseases, such as obesity and type II diabetes, have increased dramatically. Obesity and abnormal insulin level are associated with a wide variety of health problems including a markedly increased risk for type II diabetes, fatty liver, hepato-biliary and gallbladder diseases, cardiovascular pathologies, neurodegenerative disorders, asthma and a variety of cancers. The development of therapeutic antibodies has evolved over the past decades into a mainstay of therapeutic options for patients with inflammatory diseases and cancer, while other indication areas such as metabolic diseases have so far only been rarely addressed. Although therapeutic antibodies might have advantages over current type II diabetes treatments like favorable serum half-life and high specificity, their development is also likely to face obstacles. For example the technical feasibility of antibody generation against G protein coupled receptors and transporters is challenging, patient compliance for a likely needle application might be limited, bioavailability in organs involved in the pathogenesis like the brain might be suboptimal and reimbursement issues for high treatment costs have to be taken into account. The current review focuses on the pathogenesis and standard therapeutic approaches as well as antibodies in development and potential antibody targets for type II diabetes.     

Chest diseases: benefits of hyperbaric oxygen therapy in infectious disease

The Scientific Board of the California Medical Association presents the following inventory of items of progress in chest diseases. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in chest diseases that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Chest Diseases of the California Medical Association and the summaries were prepared under its direction.     

Can metabolomics be used for assessing nutritive-dependent human diseases?

Metabolomic approaches are taking place within emerging technologies that share the focus to unravel unexpected effects in classical biological experiments, for example mutant/wild type comparisons. This review highlights the possibility of metabolomics going beyond this stage and comparing the onset and the pathogenesis of complex diseases, such as type 2 diabetes mellitus, in large scale projects that might reach out to compare different populations and different nutritional diets and interventions. The steps of validation that are needed to pursue such projects are described, and the range of analytical and computational approaches that can be utilized are discussed. Using type 2 diabetes mellitus, it is emphasized that there is a high economic and scientific need to reliably diagnose and predict metabolic diseases in a cost effective manner. This revised version was published online in June 2006 with corrections to the Cover Date.     

Adding biotic complexity alters the metabolic benefits of mutualism

Mutualism is ubiquitous in nature and plays an integral role in most communities. To predict the eco‐evolutionary dynamics of mutualism it is critical to extend classic pair‐wise analysis to include additional species. We investigated the effect of adding a third species to a pair‐wise mutualism in a spatially structured environment. We tested the hypotheses that selection for costly excretions in a focal population (i) decreases when an exploiter is added (ii) increases when a third mutualist is added relative to the pair‐wise scenario. We assayed the selection acting on Salmonella enterica when it exchanges methionine for carbon in an obligate mutualism with an auxotrophic Escherichia coli. A third bacterium, Methylobacterium extorquens, was then added and acted either as an exploiter of the carbon or third obligate mutualist depending on the nitrogen source. In the tripartite mutualism M. extorquens provided nitrogen to the other species. Contrary to our expectations, adding an exploiter increased selection for methionine excretion in S. enterica. Conversely, selection for cooperation was lower in the tripartite mutualism relative to the pair‐wise system. Genome‐scale metabolic models helped identify the mechanisms underlying these changes in selection. Our results highlight the utility of connecting metabolic mechanisms and eco‐evolutionary dynamics.     

基于UPLC-QTOF-MS代谢组学研究灰树花发酵的代谢差异

为了解天麻苦荞复配液的添加对灰树花深层发酵过程中代谢产物的差异性,采用超高效液相色谱-四级杆串联飞行时间质谱（UPLC-QTOF-MS）技术结合多变量统计分析方法,对发酵7d的灰树花菌丝体细胞代谢物进行分析。主成分（PCA）模型显示添加天麻苦荞复配液的菌丝体细胞与对照组菌丝体细胞相比代谢产物差异明显（P<0.05）,通过正交偏最小二乘判别分析（OPLS-DA）,以VIP（varible importance in the projection）>1和P<0.05为条件进行筛选和鉴定得到44种差异代谢物,包括糖类6种、氨基酸类13种、维生素类5种、核苷酸类7种、有机酸类10种、脂肪酸类3种。其中,与对照组相比鼠李糖、D-半乳糖、D-甘露醇、果糖-6-磷酸等7种物质含量显著下调,D-木糖醇、异亮氨酸、赖氨酸、泛酸、二十二碳六烯酸、D-葡萄糖醛酸、琥珀酸等37种物质含量显著上调。通过对差异代谢物进行通路分析,得到具有显著影响的代谢通路14条,推测了灰树花胞外多糖合成通路。由此推断天麻苦荞复配液的添加对灰树花胞外多糖的增效作用和提升营养品质的原因,为今后深层次研究外源添加物对灰树花发酵过程的影响提供理论依据。     

Mediterranean diet and metabolic diseases

PURPOSE OF REVIEW: The objective of this article is to present evidence illustrating the relationship between Mediterranean diets and metabolic diseases, including obesity, type 2 diabetes, and the metabolic syndrome, and to briefly discuss potential mechanisms by which these diets can help in disease prevention and treatment. RECENT FINDINGS: Although the Mediterranean diet has long been celebrated for its impact on cardiovascular health, mounting evidence indicates a favorable effect on obesity and type 2 diabetes, as well. While health promotion strategies aimed at preventing adult obesity are emphasizing components of Mediterranean dietary patterns, a role for Mediterranean diets in attenuating the inflammatory burden associated with type 2 diabetes is also emerging. Moreover, a lower prevalence of the metabolic syndrome is associated with dietary patterns rich in fruits, vegetables, whole grains, dairy products, and unsaturated fats. Both epidemiological and interventional studies have revealed a protective effect of the Mediterranean diet against mild chronic inflammation and its metabolic complications. SUMMARY: Mounting evidence suggests that Mediterranean diets could serve as an anti-inflammatory dietary pattern, which could help fighting diseases that are related to chronic inflammation, including visceral obesity, type 2 diabetes and the metabolic syndrome.     

Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation

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Stable isotope-assisted metabolomics to detect metabolic flux changes in mammalian cell cultures

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Highlights► Stable isotope-assisted metabolomics is powerful to determine metabolic fluxes. ► Stable isotope-assisted metabolomics is more complex for mammalian cell cultures. ► Biotechnological processes can be improved by assessing metabolic flux changes. ► Metabolic flux analysis is an attractive tool for toxicity studies. ► There is a huge potential for future applications on mammalian systems.     

Mitochondrial ion transport pathways: Role in metabolic diseases

Mitochondria are the central coordinators of energy metabolism and alterations in their function and number have long been associated with metabolic disorders such as obesity, diabetes and hyperlipidemias. Since oxidative phosphorylation requires an electrochemical gradient across the inner mitochondrial membrane, ion channels in this membrane certainly must play an important role in the regulation of energy metabolism. However, in many experimental settings, the relationship between the activity of mitochondrial ion transport and metabolic disorders is still poorly understood. This review briefly summarizes some aspects of mitochondrial H⁺ transport (promoted by uncoupling proteins, UCPs), Ca²⁺ and K⁺ uniporters which may be determinant in metabolic disorders.