Constraint-based models such as flux balance analysis （FBA） are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution an...Constraint-based models such as flux balance analysis （FBA） are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term‘noise＇, and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states.展开更多
Cytoscape is often used for visualization and analysis of metabolic pathways.For example,based on KEGG data,a reader for KEGG Markup Language(KGML)is used to load files into Cytoscape.However,although multiple genes c...Cytoscape is often used for visualization and analysis of metabolic pathways.For example,based on KEGG data,a reader for KEGG Markup Language(KGML)is used to load files into Cytoscape.However,although multiple genes can be responsible for the same reaction,the KGMLreader KEGGScape only presents the first listed gene in a network node for a given reaction.This can lead to incorrect interpretations of the pathways.Our new method,FunHoP,shows all possible genes in each node,making the pathways more complete.FunHoP collapses all genes in a node into one measurement using read counts from RNA-seq.Assuming that activity for an enzymatic reaction mainly depends upon the gene with the highest number of reads,and weighting the reads on gene length and ratio,a new expression value is calculated for the node as a whole.Differential expression at node level is then applied to the networks.Using prostate cancer as model,we integrate RNA-seq data from two patient cohorts with metabolism data from literature.Here we show that FunHoP gives more consistent pathways that are easier to interpret biologically.Code and documentation for running FunHoP can be found at https://github.com/kjerstirise/FunHoP.展开更多
[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a...[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a guide,we simulated pyruvate production of E.coli,screened key genes in metabolic pathways,and developed gene editing procedures accordingly.We knocked out the acetate kinase gene ackA,phosphate acetyltransferase gene pta,alcohol dehydrogenase adhE,glycogen synthase gene glgA,glycogen phosphorylase gene glgP,phosphoribosyl pyrophosphate(PRPP)synthase gene prs,ribose 1,5-bisphosphate phosphokinase gene phnN,and transporter encoding gene proP.Furthermore,we knocked in the transporter encoding gene ompC,flavonoid toxin gene fldA,and D-serine ammonia lyase gene dsdA.[Results]A shake flask process with the genetically edited mutant strain MG1655-6-2 under anaerobic conditions produced pyruvate at a titer of 10.46 g/L and a yield of 0.69 g/g.Metabolomic analysis revealed a significant increase in the pyruvate level in the fermentation broth,accompanied by notable decreases in the levels of certain related metabolic byproducts.Through 5 L fed-batch fermentation and an adaptive laboratory evolution,the strain finally achieved a pyruvate titer of 45.86 g/L.[Conclusion]This study illustrated the efficacy of a gene editing strategy predicted by a genome-scale metabolic network model in enhancing pyruvate accumulation in E.coli under anaerobic conditions and provided novel insights for microbial metabolic engineering.展开更多
The energy substances(mainly carbohydrates and fats)are the basis and guarantee of life activity,especially the oxidative phosphorylation for energy supply.However,excessive absorption and accumulation of these substa...The energy substances(mainly carbohydrates and fats)are the basis and guarantee of life activity,especially the oxidative phosphorylation for energy supply.However,excessive absorption and accumulation of these substances can lead to metabolic diseases such as obesity,hyperlipidemia,diabetes,and cancers.A large amount of studies demonstrate that G protein-coupled receptors(GPCRs)play a key role in identification and absorption of energy substances,and the signaling network of nerves,immune,and endocrine regulates their storage and utilization.The gastrointestinal mucus layer not only identifies these substances through identification in diet components but also transfers immune,metabolic,and endocrine signals of hormones,cytokines,and chemokines by promoting interactions between receptors and ligands.These signaling molecules are transferred to corresponding organs,tissues,and cells by the circulatory system,and cell activity is regulated by amplifying of cell signals that constitute the wireless communication network among cells in the body.Absorption,accumulation,and utilization of energy substances in the body obey the law of energy conservation.Energy is stored in the form of fat,and meets the demand of body via two coupled mechanisms:catabolism and oxidative phosphorylation.Under normal physiological conditions,fat consumption involves ketone body metabolism through the circulatory system and glucose consumption requires blood lactic acid cycle.Accumulation of excessive energy leads to the abnormal activation of mammalian target of rapamycin(mTOR),thus promoting the excretion of glucose or glycogen in the form of blood glucose and urine glucose.Alternatively,the body cancels the intercellular contact inhibition and promotes cell proliferation to induce carcinogenesis,which can induce the consumption of large amounts of glucose.Intercellular communication is performed by signaling molecules via sensing,absorption,accumulation,and utilization of energy substances,and anabolism and catabolism are controlled by the central metabolic pathway.Therefore,slower catabolism will result in longer life expectancy,whereas faster catabolism results in shorter life expectancy.Energy substances in diet influence the balance between energy and metabolism in the body through the sensing function of the gastrointestinal system at two levels:cellular communication network and metabolic network.The present review of studies aims to strengthen our knowledge on cellular communication and metabolic networks to offer a dietary guidance on the metabolism and communication role of various foods.展开更多
Metabolic network construction plays a pivotal role in unraveling the regulatory mechanism of biological activities,although it often proves to be challenging and labor-intensive,particularly with non-model organisms....Metabolic network construction plays a pivotal role in unraveling the regulatory mechanism of biological activities,although it often proves to be challenging and labor-intensive,particularly with non-model organisms.In this study,we develop a computational approach that employs reaction models based on the structure-guided chemical modification and related compounds to construct a metabolic network in wheat.This construction results in a comprehensive structure-guided network,including 625 identified metabolites and additional 333 putative reactions compared with the Kyoto Encyclopedia of Genes and Genomes database.Using a combination of gene annotation,reaction classification,structure similarity,and correlations from transcriptome and metabolome analysis,a total of 229 potential genes related to these reactions are identified within this network.To validate the network,the functionality of a hydroxycinnamoyltransferase(TraesCS3D01G314900)for the synthesis of polyphenols and a rhamnosyltransferase(TraesCS2D01G078700)for the modification of flavonoids are verified through in vitro enzymatic studies and wheat mutant tests,respectively.Our research thus supports the utility of structure-guided chemical modification as an effective tool in identifying causal candidate genes for constructing metabolic networks and further in metabolomic genetic studies.展开更多
Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable significance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is u...Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable significance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39%of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.展开更多
OBJECTIVE One of the long-expected goals of genome-scale metabolic modeling is to evaluate the influence of the perturbed enzymes to the yield of an expected end product.METHDOS Metabolic control analysis(MCA)performs...OBJECTIVE One of the long-expected goals of genome-scale metabolic modeling is to evaluate the influence of the perturbed enzymes to the yield of an expected end product.METHDOS Metabolic control analysis(MCA)performs such role to calculate the sensitivity of flux change upon that of enzymes under the framework of ordinary differential equation(ODE)models,which are restricted in small-scale networks and require explicit kinetic parameters.The constraint-based models,like flux balance analysis(FBA),lack of the room of performing MCA because they are parameters-free.In this study,we developed a hyper-cube shrink algorithm(HCSA)to incorporate the enzymatic properties to the FBA model by introducing a pair of parameters for each reaction.Our algorithm was able to handle not only prediction of knockout strains but also strains with an adjustment of expression level of certain enzymes.RESULTS We first showed the concept by applying HCSA to a simplest three-nodes network.Then we show the HCSA possesses Michaelis-Menten like behaviors characterized by steady state of ODE.We obtained good prediction of a synthetic network in Saccharomyces cerevisiae producing voilacein and analogues.Finally we showed its capability of predicting the flux distribution in genome-scale networks by applying it to sporulation in yeast.CONCLUSION We have developed an algorithm the impact on fluxes when certain enzymes were inhibited or activated.It provides us a powerful tool to evaluate the consequences of enzyme inhibitor or activator.展开更多
We investigate the emergence of scale-free behaviour in a traffic system by using the NaSch model to simulate the evolution of traffic flow. A kind of evolution networks has been proposed, which is based on the evolut...We investigate the emergence of scale-free behaviour in a traffic system by using the NaSch model to simulate the evolution of traffic flow. A kind of evolution networks has been proposed, which is based on the evolution of the traffic flow. The network growth does not take into account preferential attachment, and the attachment of new node is independent of degree. The simulation results demonstrate that the output distribution of links is well described by a scale-free distribution.展开更多
OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dah...OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.展开更多
Nitrous oxide is one of the most commonly used inhalational anesthetic agents used in practice.It is a cost-effective,pleasant,safe,and versatile anesthetic agent with many desirable properties like good quality analg...Nitrous oxide is one of the most commonly used inhalational anesthetic agents used in practice.It is a cost-effective,pleasant,safe,and versatile anesthetic agent with many desirable properties like good quality analgesia,decreased awareness,accelerated induction and recovery from anesthesia,and reduced utilization of other expensive inhalational agents with potential cost savings.The use of nitrous oxide has been questioned by a lot of studies and case reports perceiving its adverse systemic,hematological,immune,and neurologic adverse effects.However,the literature in the recent past has tried to resolve the controversies related to its use.The concerns over an increase in cardiovascular complications and mortality following nitrous oxide use have been negated by recent data.However,its use in certain vulnerable populations like children with cobalamin and folate deficiency or defects in their metabolic pathways remains a cause of concern for its toxic effects.In this narrative review,we aim to discuss the pharmacological properties of nitrous oxide,the potential advantages and drawbacks of the use of nitrous oxide in children,address the neurodevelopmental and other systemic effects,and throw light on the evidence regarding the safety of nitrous oxide use and its current role in pediatric procedural sedation and anesthesia practice.The literature related to its use in the pediatric population for painful procedures and surgeries has been summarized.展开更多
The stoichiometric matrix of a simplified metabolic network inBacillus Subtillis was constructed from the flux balance equations,which were used for reconciliation of the measured rates anddetermination of the inner m...The stoichiometric matrix of a simplified metabolic network inBacillus Subtillis was constructed from the flux balance equations,which were used for reconciliation of the measured rates anddetermination of the inner metabolic rates. Thus more reliableresults of the true and empirical maintenance coefficients wereobtained. The true maintenance coefficient is linearly related to thespecific growth rate and changes with the P/O ratio. The measuredbiomass yield of adenosine triphosphate (ATP) is also linearlyrelated to the P/O ratio.展开更多
Ginseng has high medicinal value.Different ginseng have different benefits,but how they work in the body’s immune metabolism is unclear.in this study,different types of ginseng were ingested and serum cytokines,some ...Ginseng has high medicinal value.Different ginseng have different benefits,but how they work in the body’s immune metabolism is unclear.in this study,different types of ginseng were ingested and serum cytokines,some metabolite concentrations and metabolic enzyme expression levels were measured.intercellular communication networks and metabolic networks were constructed and analyzed for correlation.the results show that the effect of wild ginseng on cytokine secretion and metabolic pathway fluxes was greater.an intake of garden ginseng activated aerobic glycolysis to enhance immunity,while an intake of forest ginseng and wild ginseng increased pentose phosphate pathway,tricarboxylic acid cycle,and oxidative phosphorylation activity to promote immunity.therefore,the intake of 500 mg/person of forest ginseng or 100 mg/person of wild ginseng was beneficial to health.the study of cytokines and metabolic networks may also provide new ideas for exploring the effects of ginseng and others on the body.展开更多
TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organ...TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organisms were curated from UniProt functional annotation. A unique feature of TSdb is that all the substrates are mapped to identifiers from the KEGG Ligand com- pound database. Thus, TSdb links current metabolic pathway schema with compound transporter systems via the shared compounds in the pathways. Furthermore, all the transporter substrates in TSdb are classified according to their biochemical properties, biological roles and subcellular localizations. In addition to the functional annotation of transporters, extensive compound annotation that includes inhibitor information from the KEGG Ligand and BRENDA databases has been integrated, making TSdb a useful source for the discovery of potential inhibitory mechanisms linking transporter substrates and metabolic enzymes. User-friendly web interfaces are designed for easy access, query and download of the data. Text and BLAST searches against all transporters in the database are provided. We will regularly update the substrate data with evidence from new publications.展开更多
Classical Petri net has been applied into biological analysis, especially as a qualitative model for biochemical pathways analysis, but lack of the ability for quantitative kinetic simulations. In our study, we presen...Classical Petri net has been applied into biological analysis, especially as a qualitative model for biochemical pathways analysis, but lack of the ability for quantitative kinetic simulations. In our study, we presented an integra- tion work of the qualitative model--Petri nets with the quantitative approach-ordinary differential equations （ODEs） for the modeling and analysis of metabolic networks. As an application of our study, the computational modeling of arachidonic acid （AA） biochemical network was provided. A Petri net was set up to present the constraint-based dynamic simulations on AA metabolic network combined with the validated ODEs model. Furthermore, Graphics Processing Unit （GPU） was adopted to accelerate the calculation of kinetic parameters unavailable from experi- ments. Our results have indicated that the proposed simulation method was practicable and useful with GPU accel- eration, and provides new clues for the large-scale qualitative and quantitative models of biochemical networks.展开更多
Metabolic network models have become increasingly precise and accurate as the most widespread and practical digital representations of living cells.The prediction functions were significantly expanded by integrating c...Metabolic network models have become increasingly precise and accurate as the most widespread and practical digital representations of living cells.The prediction functions were significantly expanded by integrating cellular resources and abiotic constraints in recent years.However,if unreasonable modeling methods were adopted due to a lack of consideration of biological knowledge,the conflicts between stoichiometric and other constraints,such as thermodynamic feasibility and enzyme resource availability,would lead to distorted predictions.In this work,we investigated a prediction anomaly of EcoETM,a constraints-based metabolic network model,and introduced the idea of enzyme compartmentalization into the analysis process.Through rational combination of reactions,we avoid the false prediction of pathway feasibility caused by the unrealistic assumption of free intermediate metabolites.This allowed us to correct the pathway structures of L-serine and L-tryptophan.A specific analysis explains the application method of the EcoETM-like model and demonstrates its potential and value in correcting the prediction results in pathway structure by resolving the conflict between different constraints and incorporating the evolved roles of enzymes as reaction compartments.Notably,this work also reveals the trade-off between product yield and thermodynamic feasibility.Our work is of great value for the structural improvement of constraints-based models.展开更多
Cotton(Gossypium hirsutum L.)is one of the world’s most important commercial crops.However,the dynamics of metabolite abundance and potential regulatory networks throughout its life cycle remain poorly understood.In ...Cotton(Gossypium hirsutum L.)is one of the world’s most important commercial crops.However,the dynamics of metabolite abundance and potential regulatory networks throughout its life cycle remain poorly understood.In this study,we developed a cotton metabolism regulatory network(CMRN)that spans various developmental stages and encompasses 2138 metabolites and 90309 expressed genesin upland cotton.By integrating high-resolution spatiotemporal metabolome and transcriptome data,we identified 1958 differentially accumulated metabolites and 13597 co-expressed differentially expressed genes between the dwarf mutant pagoda1 and its wild-type counterpart Zhongmiansuo 24.These metabolites and genes were categorized into seven clusters based on tissue-specific accumulation patterns and gene expression profiles across different developmental stages.Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed significant differential enrichment in the fatty acid elongation pathway,particularly in fibers.The differential involvement of genes and metabolites in very-long-chain fatty acid(VLCFA)synthesis led to the identification of GhKCS1b_Dt as a key gene.Overexpression of GhKCS1b_Dt significantly promoted fiber elongation,while its silencing markedly inhibited cotton fiber growth,affirming its positive regulatory role in fiber elongation.This dataset provides a valuable resource for further research into metabolic pathways and gene regulatory networks,offering novel insights for advancing cotton breeding strategies.展开更多
Although numerous studies have focused on phytohormones in specific organs or tissues at different development stages or under various abiotic and biotic stress conditions,our understanding of the distribution and rel...Although numerous studies have focused on phytohormones in specific organs or tissues at different development stages or under various abiotic and biotic stress conditions,our understanding of the distribution and relative abundance of phytohormones throughout the entire life cycle of plants remains insufficient.Here,we present a phytohormone atlas resource obtained from the quantitative analysis of eight major classes of phytohormones,comprising a total of 40 hormone-related compounds,throughout the complete life cycle of wheat.In combination with transcriptome analysis,we established a wheat phytohormone metabolic regulatory network(WPMRN).Using the WPMRN dataset and Gene Ontology enrichment analysis,we swiftly characterized the function of TaLOG5-B1 in cytokinin biosynthesis.Furthermore,a detailed investigation of the WPMRN dataset uncovered transcription factor-mediated co-regulatory mechanisms among different classes of phytohormones.We focused specifically on the metabolic regulation of cytokinin and jasmonic acid,and functionally characterized the genes TaLOG3-D1 and TaAOS-D1 that are involved in the biosynthesis of these phytohormones,respectively,along with their regulatory transcription factor genes TaDOF3A and TaDOF5.6B.The functions of these genes were validated in transgenic plants,revealing their ability to co-regulate radicle length.These findings serve as a case study that highlights the utility of this resource for studying phytohormone metabolic regulatory networks in cereal crops and for gaining insights into the roles of phytohormones in enhancing agronomic traits.展开更多
Soybean[Glycine max（L.） Merr.]is one of the world＇s major crops,and soybean seeds are a rich and important resource for proteins and oils.While ＂omics＂ studies,such as genomics,transcriptomics,and proteomics,have...Soybean[Glycine max（L.） Merr.]is one of the world＇s major crops,and soybean seeds are a rich and important resource for proteins and oils.While ＂omics＂ studies,such as genomics,transcriptomics,and proteomics,have been widely applied in soybean molecular research,fewer metabolomic studies have been conducted for largescale detection of low molecular weight metabolites,especially in soybean seeds.In this study,we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry.One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed.Among the 169 detected metabolites,104 were found to be significantly variable in their levels across tested cultivars.Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified,and metabolitemetabolite correlation analysis revealed some significant associations within the same or among different metabolite groups.Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.展开更多
Microorganisms played a key role in developing the flavor quality,while few studies focused on the relationship between microbial diversity and flavor quality of dry-cured boneless ham.To explore the relationship,sens...Microorganisms played a key role in developing the flavor quality,while few studies focused on the relationship between microbial diversity and flavor quality of dry-cured boneless ham.To explore the relationship,sensory evaluation,lipases,microorganism communities,free fatty acids and volatile compounds were investigated in dry-cured boneless ham with different quality grades(NS,WS and GS groups);the correlation between cored microbes and crucial volatiles was further evaluated by metabolic network analysis.GS group showed the highest scores in aroma and overall acceptance among three groups.The highest values of phospholipase activities(7.88 U*g^(−1) protein)were shown in GS group,while the lowest values of TBARS(0.93 mg/kg)were observed in GS among three groups.High-throughput sequencing revealed that fungi showed the most various among three groups;Xerochrysium,Aspergillus,Penicillium and Debaryomyces were the most genera in GS.SPME-GC-MS revealed that GS showed higher contents and numbers in volatiles than other groups;aldehydes and furans were intensely response to the variations of volatiles among these groups.Metabolic pathway further revealed that several key species derived from Penicillium and Aspergillus accelerated the formation of volatiles byβ-lipoxidation and Strecker degradation.These results indicated that molds could be the major contributors in developing and differentiating the flavor quality of Chinese dry-cured boneless ham.展开更多
Archaea,one of the three domains of life along with Bacteria and Eukarya,contains ancient life forms such as methanogen that are observed today on Earth,and one lineage Asgard archaea is also considered the closest an...Archaea,one of the three domains of life along with Bacteria and Eukarya,contains ancient life forms such as methanogen that are observed today on Earth,and one lineage Asgard archaea is also considered the closest ancestor of Eukarya.Recently,with the development of interdisciplinary studies from Earth and Life sciences,archaeal organisms are considered to play pivotal roles in geochemical cycling in nature.However,our understanding of the attributes,origin and evolution,geochemical and ecological functions of Archaea is hampered by the scarcity of archaeal isolates,which has represented a challenge to researchers for the last 40 years.Cultivation-independent sequencing and phylogenomic analyses have demonstrated a considerable diversity of Archaea with more than 20 novel phyla.However,only four archaeal phyla have cultured representatives,leaving large gaps in our knowledge of the metabolic capabilities and ecological functions of the majority of archaeal strains identified exclusively by DNA sequencing.In this review,we summarize the discovery and development of archaeal research,highlight the knowledge gap between uncultured and cultured archaeal microbes,and call on the importance of devoting greater research efforts to archaeal cultivation.Finally,we outlined new ideas and strategic approaches,namely,(1)genome-based methods,(2)microbial network information-based methods,(3)genome-scale model-guided methods,and(4)machine learning methods,to enable the cultivation of uncultivated archaeal microbes using accumulated high-throughput sequencing data.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No 10721403)the MOST of China (Grant No2009CB918500)the National Basic Research Program of China (Grant Nos 2006CB910706 and 2007CB814800)
文摘Constraint-based models such as flux balance analysis （FBA） are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term‘noise＇, and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states.
基金supported by a PhD position from Enabling Technologies, Norwegian University of Science and Technology (NTNU)the Department of Clinical and Molecular Medicine (IKOM), NTNU to KR+5 种基金the Liaison Committee between the Central Norway Regional Health Authority (RHA) and the NTNU to MBREuropean Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant No. 758306) gave funding to MBTFunding support for MPC_Transcriptome sequencing to identify non-coding RNAs in prostate cancer was provided through the NIH Prostate SPORE (Grant Nos. P50CA69568 and R01 R01CA132874)the Early Detection Research Network (Grant No. U01 CA111275)the Department of Defense Grant (Grant No. W81XWH-11-1-0331)the National Center for Functional Genomics (Grant No. W81XWH-11-1-0520)
文摘Cytoscape is often used for visualization and analysis of metabolic pathways.For example,based on KEGG data,a reader for KEGG Markup Language(KGML)is used to load files into Cytoscape.However,although multiple genes can be responsible for the same reaction,the KGMLreader KEGGScape only presents the first listed gene in a network node for a given reaction.This can lead to incorrect interpretations of the pathways.Our new method,FunHoP,shows all possible genes in each node,making the pathways more complete.FunHoP collapses all genes in a node into one measurement using read counts from RNA-seq.Assuming that activity for an enzymatic reaction mainly depends upon the gene with the highest number of reads,and weighting the reads on gene length and ratio,a new expression value is calculated for the node as a whole.Differential expression at node level is then applied to the networks.Using prostate cancer as model,we integrate RNA-seq data from two patient cohorts with metabolism data from literature.Here we show that FunHoP gives more consistent pathways that are easier to interpret biologically.Code and documentation for running FunHoP can be found at https://github.com/kjerstirise/FunHoP.
基金supported by the Hebei Provincial Key Research and Development Project(21372803D)。
文摘[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a guide,we simulated pyruvate production of E.coli,screened key genes in metabolic pathways,and developed gene editing procedures accordingly.We knocked out the acetate kinase gene ackA,phosphate acetyltransferase gene pta,alcohol dehydrogenase adhE,glycogen synthase gene glgA,glycogen phosphorylase gene glgP,phosphoribosyl pyrophosphate(PRPP)synthase gene prs,ribose 1,5-bisphosphate phosphokinase gene phnN,and transporter encoding gene proP.Furthermore,we knocked in the transporter encoding gene ompC,flavonoid toxin gene fldA,and D-serine ammonia lyase gene dsdA.[Results]A shake flask process with the genetically edited mutant strain MG1655-6-2 under anaerobic conditions produced pyruvate at a titer of 10.46 g/L and a yield of 0.69 g/g.Metabolomic analysis revealed a significant increase in the pyruvate level in the fermentation broth,accompanied by notable decreases in the levels of certain related metabolic byproducts.Through 5 L fed-batch fermentation and an adaptive laboratory evolution,the strain finally achieved a pyruvate titer of 45.86 g/L.[Conclusion]This study illustrated the efficacy of a gene editing strategy predicted by a genome-scale metabolic network model in enhancing pyruvate accumulation in E.coli under anaerobic conditions and provided novel insights for microbial metabolic engineering.
文摘The energy substances(mainly carbohydrates and fats)are the basis and guarantee of life activity,especially the oxidative phosphorylation for energy supply.However,excessive absorption and accumulation of these substances can lead to metabolic diseases such as obesity,hyperlipidemia,diabetes,and cancers.A large amount of studies demonstrate that G protein-coupled receptors(GPCRs)play a key role in identification and absorption of energy substances,and the signaling network of nerves,immune,and endocrine regulates their storage and utilization.The gastrointestinal mucus layer not only identifies these substances through identification in diet components but also transfers immune,metabolic,and endocrine signals of hormones,cytokines,and chemokines by promoting interactions between receptors and ligands.These signaling molecules are transferred to corresponding organs,tissues,and cells by the circulatory system,and cell activity is regulated by amplifying of cell signals that constitute the wireless communication network among cells in the body.Absorption,accumulation,and utilization of energy substances in the body obey the law of energy conservation.Energy is stored in the form of fat,and meets the demand of body via two coupled mechanisms:catabolism and oxidative phosphorylation.Under normal physiological conditions,fat consumption involves ketone body metabolism through the circulatory system and glucose consumption requires blood lactic acid cycle.Accumulation of excessive energy leads to the abnormal activation of mammalian target of rapamycin(mTOR),thus promoting the excretion of glucose or glycogen in the form of blood glucose and urine glucose.Alternatively,the body cancels the intercellular contact inhibition and promotes cell proliferation to induce carcinogenesis,which can induce the consumption of large amounts of glucose.Intercellular communication is performed by signaling molecules via sensing,absorption,accumulation,and utilization of energy substances,and anabolism and catabolism are controlled by the central metabolic pathway.Therefore,slower catabolism will result in longer life expectancy,whereas faster catabolism results in shorter life expectancy.Energy substances in diet influence the balance between energy and metabolism in the body through the sensing function of the gastrointestinal system at two levels:cellular communication network and metabolic network.The present review of studies aims to strengthen our knowledge on cellular communication and metabolic networks to offer a dietary guidance on the metabolism and communication role of various foods.
基金supported by the Young Top-notch Talent Cultivation Program of Hubei Province,the Natural Science Foundation for Distinguished Young Scientists of Hubei Province(2021CFA058)the First-Class Discipline Construction Funds of College of Plant Science and Technology,Huazhong Agricultural University(2023ZKPY005).
文摘Metabolic network construction plays a pivotal role in unraveling the regulatory mechanism of biological activities,although it often proves to be challenging and labor-intensive,particularly with non-model organisms.In this study,we develop a computational approach that employs reaction models based on the structure-guided chemical modification and related compounds to construct a metabolic network in wheat.This construction results in a comprehensive structure-guided network,including 625 identified metabolites and additional 333 putative reactions compared with the Kyoto Encyclopedia of Genes and Genomes database.Using a combination of gene annotation,reaction classification,structure similarity,and correlations from transcriptome and metabolome analysis,a total of 229 potential genes related to these reactions are identified within this network.To validate the network,the functionality of a hydroxycinnamoyltransferase(TraesCS3D01G314900)for the synthesis of polyphenols and a rhamnosyltransferase(TraesCS2D01G078700)for the modification of flavonoids are verified through in vitro enzymatic studies and wheat mutant tests,respectively.Our research thus supports the utility of structure-guided chemical modification as an effective tool in identifying causal candidate genes for constructing metabolic networks and further in metabolomic genetic studies.
基金supported by the National Natural Science Foundation of China (Grant Nos.: 81530095 and 81673591)Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.: XDA12020348)+1 种基金National Standardization of Traditional Chinese Medicine Project (Grant No.: ZYBZH-K-LN-01)Science and Technology Commission Foundation of Shanghai (Grant No.: 15DZ0502800)
文摘Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable significance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39%of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.
基金The project supported by 985 Startup Funding in PKU
文摘OBJECTIVE One of the long-expected goals of genome-scale metabolic modeling is to evaluate the influence of the perturbed enzymes to the yield of an expected end product.METHDOS Metabolic control analysis(MCA)performs such role to calculate the sensitivity of flux change upon that of enzymes under the framework of ordinary differential equation(ODE)models,which are restricted in small-scale networks and require explicit kinetic parameters.The constraint-based models,like flux balance analysis(FBA),lack of the room of performing MCA because they are parameters-free.In this study,we developed a hyper-cube shrink algorithm(HCSA)to incorporate the enzymatic properties to the FBA model by introducing a pair of parameters for each reaction.Our algorithm was able to handle not only prediction of knockout strains but also strains with an adjustment of expression level of certain enzymes.RESULTS We first showed the concept by applying HCSA to a simplest three-nodes network.Then we show the HCSA possesses Michaelis-Menten like behaviors characterized by steady state of ODE.We obtained good prediction of a synthetic network in Saccharomyces cerevisiae producing voilacein and analogues.Finally we showed its capability of predicting the flux distribution in genome-scale networks by applying it to sporulation in yeast.CONCLUSION We have developed an algorithm the impact on fluxes when certain enzymes were inhibited or activated.It provides us a powerful tool to evaluate the consequences of enzyme inhibitor or activator.
基金Supported by the National Natural Science Foundation of China under Grant No 70471088, and the Science and Technology Foundation of Beijing Jiaotong University under Grant No 2004SM026.
文摘We investigate the emergence of scale-free behaviour in a traffic system by using the NaSch model to simulate the evolution of traffic flow. A kind of evolution networks has been proposed, which is based on the evolution of the traffic flow. The network growth does not take into account preferential attachment, and the attachment of new node is independent of degree. The simulation results demonstrate that the output distribution of links is well described by a scale-free distribution.
基金National Major Natural Science:Study on the Dose-effect Relationship and Compatibility Mechanism of Core Medicine in Taohe Chengqi Decoction Prescription on "Removing Stasis And Dissipating Heat" of Taoren Rhubarb (No. 81973592)Project of the Administration of Traditional Chinese Medicine of Shaanxi Province:Study on the Compatibility of the Classic Prescription Taohe Chengqi Decoction "Expelling Stasis And Expelling Heat" Based on Drug Interaction (2021-GJ-JC004)Supported by Discipline Innovation Team Project on Quality Evaluation and Resource Development of "Qin Medicine",Shaanxi University of Chinese Medicine (2019-QN01)。
文摘OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.
文摘Nitrous oxide is one of the most commonly used inhalational anesthetic agents used in practice.It is a cost-effective,pleasant,safe,and versatile anesthetic agent with many desirable properties like good quality analgesia,decreased awareness,accelerated induction and recovery from anesthesia,and reduced utilization of other expensive inhalational agents with potential cost savings.The use of nitrous oxide has been questioned by a lot of studies and case reports perceiving its adverse systemic,hematological,immune,and neurologic adverse effects.However,the literature in the recent past has tried to resolve the controversies related to its use.The concerns over an increase in cardiovascular complications and mortality following nitrous oxide use have been negated by recent data.However,its use in certain vulnerable populations like children with cobalamin and folate deficiency or defects in their metabolic pathways remains a cause of concern for its toxic effects.In this narrative review,we aim to discuss the pharmacological properties of nitrous oxide,the potential advantages and drawbacks of the use of nitrous oxide in children,address the neurodevelopmental and other systemic effects,and throw light on the evidence regarding the safety of nitrous oxide use and its current role in pediatric procedural sedation and anesthesia practice.The literature related to its use in the pediatric population for painful procedures and surgeries has been summarized.
基金Supported by the Key Program of National Natural Science Foundation of China (No. 20036010) and the National Science Fund for Distinguished Young Scholars (No. 20028607).
文摘The stoichiometric matrix of a simplified metabolic network inBacillus Subtillis was constructed from the flux balance equations,which were used for reconciliation of the measured rates anddetermination of the inner metabolic rates. Thus more reliableresults of the true and empirical maintenance coefficients wereobtained. The true maintenance coefficient is linearly related to thespecific growth rate and changes with the P/O ratio. The measuredbiomass yield of adenosine triphosphate (ATP) is also linearlyrelated to the P/O ratio.
基金financially supported by the National Natural Science foundation of China(31901782).
文摘Ginseng has high medicinal value.Different ginseng have different benefits,but how they work in the body’s immune metabolism is unclear.in this study,different types of ginseng were ingested and serum cytokines,some metabolite concentrations and metabolic enzyme expression levels were measured.intercellular communication networks and metabolic networks were constructed and analyzed for correlation.the results show that the effect of wild ginseng on cytokine secretion and metabolic pathway fluxes was greater.an intake of garden ginseng activated aerobic glycolysis to enhance immunity,while an intake of forest ginseng and wild ginseng increased pentose phosphate pathway,tricarboxylic acid cycle,and oxidative phosphorylation activity to promote immunity.therefore,the intake of 500 mg/person of forest ginseng or 100 mg/person of wild ginseng was beneficial to health.the study of cytokines and metabolic networks may also provide new ideas for exploring the effects of ginseng and others on the body.
基金supported by the National High Technology Research and Development Program of China (Grant Nos. 2006AA02Z334, 2006AA02Z314, 2006AA02A312 and 2007AA02Z165)the National Basic Research Program of China (Grant Nos. 2006CB910404 and 2007CB946904)support of the K. C. Wong Education Foundation, Hong Kong
文摘TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organisms were curated from UniProt functional annotation. A unique feature of TSdb is that all the substrates are mapped to identifiers from the KEGG Ligand com- pound database. Thus, TSdb links current metabolic pathway schema with compound transporter systems via the shared compounds in the pathways. Furthermore, all the transporter substrates in TSdb are classified according to their biochemical properties, biological roles and subcellular localizations. In addition to the functional annotation of transporters, extensive compound annotation that includes inhibitor information from the KEGG Ligand and BRENDA databases has been integrated, making TSdb a useful source for the discovery of potential inhibitory mechanisms linking transporter substrates and metabolic enzymes. User-friendly web interfaces are designed for easy access, query and download of the data. Text and BLAST searches against all transporters in the database are provided. We will regularly update the substrate data with evidence from new publications.
文摘Classical Petri net has been applied into biological analysis, especially as a qualitative model for biochemical pathways analysis, but lack of the ability for quantitative kinetic simulations. In our study, we presented an integra- tion work of the qualitative model--Petri nets with the quantitative approach-ordinary differential equations （ODEs） for the modeling and analysis of metabolic networks. As an application of our study, the computational modeling of arachidonic acid （AA） biochemical network was provided. A Petri net was set up to present the constraint-based dynamic simulations on AA metabolic network combined with the validated ODEs model. Furthermore, Graphics Processing Unit （GPU） was adopted to accelerate the calculation of kinetic parameters unavailable from experi- ments. Our results have indicated that the proposed simulation method was practicable and useful with GPU accel- eration, and provides new clues for the large-scale qualitative and quantitative models of biochemical networks.
基金funded by the National Key Research and Development Program of China(2018YFA0900300,2020YFA0908301)the National Natural Science Foundation of China(32201188)+1 种基金the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-CXRC-060,TSBICIP-PTJS-001,and TSBICIP-PTJS-013)the China Postdoctoral Science Foundation(2022M723341).
文摘Metabolic network models have become increasingly precise and accurate as the most widespread and practical digital representations of living cells.The prediction functions were significantly expanded by integrating cellular resources and abiotic constraints in recent years.However,if unreasonable modeling methods were adopted due to a lack of consideration of biological knowledge,the conflicts between stoichiometric and other constraints,such as thermodynamic feasibility and enzyme resource availability,would lead to distorted predictions.In this work,we investigated a prediction anomaly of EcoETM,a constraints-based metabolic network model,and introduced the idea of enzyme compartmentalization into the analysis process.Through rational combination of reactions,we avoid the false prediction of pathway feasibility caused by the unrealistic assumption of free intermediate metabolites.This allowed us to correct the pathway structures of L-serine and L-tryptophan.A specific analysis explains the application method of the EcoETM-like model and demonstrates its potential and value in correcting the prediction results in pathway structure by resolving the conflict between different constraints and incorporating the evolved roles of enzymes as reaction compartments.Notably,this work also reveals the trade-off between product yield and thermodynamic feasibility.Our work is of great value for the structural improvement of constraints-based models.
基金supported by the National Natural Science Foundation of China(grants 32441062,32360509,32301888,and 32350410409)the National Key Laboratory of Cotton Bio-breeding and Integrated Uti-lization(CBIU2024004)+4 种基金the Xinjiang Science and Technological Pro-gram(the Tianshan Talent Training Program[grant 2022TSYCCX0087]the Key Research and Development Program of Xinjiang[grant 2022B02052]the Natural Science Foundation of Xinjiang Uygur Autonomous Region[grants 2022D01E08 and 2024D01A150])the Xinjiang Science and Technology Major Project of China(grant 2024A02002)the Natural Science Foundation of Henan Province(grant 232300421253).
文摘Cotton(Gossypium hirsutum L.)is one of the world’s most important commercial crops.However,the dynamics of metabolite abundance and potential regulatory networks throughout its life cycle remain poorly understood.In this study,we developed a cotton metabolism regulatory network(CMRN)that spans various developmental stages and encompasses 2138 metabolites and 90309 expressed genesin upland cotton.By integrating high-resolution spatiotemporal metabolome and transcriptome data,we identified 1958 differentially accumulated metabolites and 13597 co-expressed differentially expressed genes between the dwarf mutant pagoda1 and its wild-type counterpart Zhongmiansuo 24.These metabolites and genes were categorized into seven clusters based on tissue-specific accumulation patterns and gene expression profiles across different developmental stages.Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed significant differential enrichment in the fatty acid elongation pathway,particularly in fibers.The differential involvement of genes and metabolites in very-long-chain fatty acid(VLCFA)synthesis led to the identification of GhKCS1b_Dt as a key gene.Overexpression of GhKCS1b_Dt significantly promoted fiber elongation,while its silencing markedly inhibited cotton fiber growth,affirming its positive regulatory role in fiber elongation.This dataset provides a valuable resource for further research into metabolic pathways and gene regulatory networks,offering novel insights for advancing cotton breeding strategies.
基金supported by the National Key Research and Development Program of China(No.2021YFF1000204)the National Key Laboratory of Crop Genetic Improvement Self-Research Program(ZW22A0302 and ZW22B0206)the Natural Science Foundation for Distinguished Young Scientists of Hubei Province(No.2021CFA058),and the Young Topnotch Talent Cultivation Program of Hubei Province。
文摘Although numerous studies have focused on phytohormones in specific organs or tissues at different development stages or under various abiotic and biotic stress conditions,our understanding of the distribution and relative abundance of phytohormones throughout the entire life cycle of plants remains insufficient.Here,we present a phytohormone atlas resource obtained from the quantitative analysis of eight major classes of phytohormones,comprising a total of 40 hormone-related compounds,throughout the complete life cycle of wheat.In combination with transcriptome analysis,we established a wheat phytohormone metabolic regulatory network(WPMRN).Using the WPMRN dataset and Gene Ontology enrichment analysis,we swiftly characterized the function of TaLOG5-B1 in cytokinin biosynthesis.Furthermore,a detailed investigation of the WPMRN dataset uncovered transcription factor-mediated co-regulatory mechanisms among different classes of phytohormones.We focused specifically on the metabolic regulation of cytokinin and jasmonic acid,and functionally characterized the genes TaLOG3-D1 and TaAOS-D1 that are involved in the biosynthesis of these phytohormones,respectively,along with their regulatory transcription factor genes TaDOF3A and TaDOF5.6B.The functions of these genes were validated in transgenic plants,revealing their ability to co-regulate radicle length.These findings serve as a case study that highlights the utility of this resource for studying phytohormone metabolic regulatory networks in cereal crops and for gaining insights into the roles of phytohormones in enhancing agronomic traits.
基金supported by the China National Transgenic Plant Special Fund(2011ZX08012-002 and 2013ZX08012-002)Innovative Research Team Fund(Ministry of Education,China)111 Project Fund(B14016)
文摘Soybean[Glycine max（L.） Merr.]is one of the world＇s major crops,and soybean seeds are a rich and important resource for proteins and oils.While ＂omics＂ studies,such as genomics,transcriptomics,and proteomics,have been widely applied in soybean molecular research,fewer metabolomic studies have been conducted for largescale detection of low molecular weight metabolites,especially in soybean seeds.In this study,we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry.One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed.Among the 169 detected metabolites,104 were found to be significantly variable in their levels across tested cultivars.Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified,and metabolitemetabolite correlation analysis revealed some significant associations within the same or among different metabolite groups.Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.
基金supported by National Natural Science Foundation of China(32101975,32022066)National Key Research and Development Program of China(2021YFD2100104)+3 种基金Modern Agricultural Technical Foundation of China(CARS-42-25)Zhejiang Province Natural Science Foundation(LQ22C200017)China Postdoctoral Foundation(2020M681806,2021T140348)Natural Science Foundation of Ningbo(20221JCGY010542).
文摘Microorganisms played a key role in developing the flavor quality,while few studies focused on the relationship between microbial diversity and flavor quality of dry-cured boneless ham.To explore the relationship,sensory evaluation,lipases,microorganism communities,free fatty acids and volatile compounds were investigated in dry-cured boneless ham with different quality grades(NS,WS and GS groups);the correlation between cored microbes and crucial volatiles was further evaluated by metabolic network analysis.GS group showed the highest scores in aroma and overall acceptance among three groups.The highest values of phospholipase activities(7.88 U*g^(−1) protein)were shown in GS group,while the lowest values of TBARS(0.93 mg/kg)were observed in GS among three groups.High-throughput sequencing revealed that fungi showed the most various among three groups;Xerochrysium,Aspergillus,Penicillium and Debaryomyces were the most genera in GS.SPME-GC-MS revealed that GS showed higher contents and numbers in volatiles than other groups;aldehydes and furans were intensely response to the variations of volatiles among these groups.Metabolic pathway further revealed that several key species derived from Penicillium and Aspergillus accelerated the formation of volatiles byβ-lipoxidation and Strecker degradation.These results indicated that molds could be the major contributors in developing and differentiating the flavor quality of Chinese dry-cured boneless ham.
基金supported by the State Key R&D Project of China(Grant No.2016YFA0601102)the China Ocean Mineral Resources R&D Association(Grant No.DY135-B2-12)+6 种基金COMRA Project DY135-B2-12the National Nature Science Foundation of China(Grant Nos.41525011,41921006,41902313,91751205&92051116)the Natural Science Foundation of Shanghai(Grant No.20ZR1428000)the Shanghai Jiao Tong University Interdisciplinary Grant(Grant No.20CX-01)Japan Society for the Promotion of Science(JSPS)(KAKENHI Grant 18H05295)This is also a contribution to the Center for Ocean Mega-Science,Chinese Academy of Sciences,the Senior User Project of RV KEXUE(Grant No.KEXUE2019GZ06)the International Center for Deep-life Investigation(IC-DLI).
文摘Archaea,one of the three domains of life along with Bacteria and Eukarya,contains ancient life forms such as methanogen that are observed today on Earth,and one lineage Asgard archaea is also considered the closest ancestor of Eukarya.Recently,with the development of interdisciplinary studies from Earth and Life sciences,archaeal organisms are considered to play pivotal roles in geochemical cycling in nature.However,our understanding of the attributes,origin and evolution,geochemical and ecological functions of Archaea is hampered by the scarcity of archaeal isolates,which has represented a challenge to researchers for the last 40 years.Cultivation-independent sequencing and phylogenomic analyses have demonstrated a considerable diversity of Archaea with more than 20 novel phyla.However,only four archaeal phyla have cultured representatives,leaving large gaps in our knowledge of the metabolic capabilities and ecological functions of the majority of archaeal strains identified exclusively by DNA sequencing.In this review,we summarize the discovery and development of archaeal research,highlight the knowledge gap between uncultured and cultured archaeal microbes,and call on the importance of devoting greater research efforts to archaeal cultivation.Finally,we outlined new ideas and strategic approaches,namely,(1)genome-based methods,(2)microbial network information-based methods,(3)genome-scale model-guided methods,and(4)machine learning methods,to enable the cultivation of uncultivated archaeal microbes using accumulated high-throughput sequencing data.
