scholarly journals Amino acid and nucleotide metabolism shape the selection of trophic levels in animals

2021 ◽  
Author(s):  
Rosemary Yu ◽  
Hao Wang ◽  
Jens Nielsen
Keyword(s):  
Lipid Metabolism ◽  
Amino Acid ◽  
Metabolic Networks ◽  
Metabolic Flux ◽  
Central Carbon Metabolism ◽  
Nucleotide Metabolism ◽  
Trophic Levels ◽  
Atp Production ◽  
Species Specific ◽  
Selection Of

What an animal eats determines its trophic level (TL) in the food web. The diet of high-TL animals is thought to contain more energy because it contains higher levels of lipids. This however has not been systematically examined in the context of comprehensive metabolic networks of different animals. Here, we reconstruct species-specific genome-scale metabolic models (GEMs) of 32 animals, and calculate the maximum ATP production per unit of food for each animal. Surprisingly, we find that ATP production is closely associated with metabolic flux through central carbon metabolism and amino acid metabolism, while correlation with lipid metabolism is low. Further, metabolism of specific amino acids and nucleotides underlie maximum ATP production from food. Our analyses indicate that amino acid and nucleotide metabolism, rather than lipid metabolism, are major contributors to the selection of animal trophic levels, demonstrating that species-level metabolic flux plays key roles in trophic interactions and evolution.

scholarly journals Nature lessons: the whitefly bacterial endosymbiont is a minimal amino acid factory with unusual energetics

2016 ◽  
Author(s):  
Jorge Calle-Espinosa ◽  
Miguel Ponce-de-Leon ◽  
Diego Santos-Garcia ◽  
Francisco J. Silva ◽  
Francisco Montero ◽  
...  
Keyword(s):  
Amino Acid ◽  
Energy Production ◽  
Metabolic Networks ◽  
Metabolic Model ◽  
Atp Production ◽  
Symbiotic Associations ◽  
Bacterial Endosymbiont ◽  
Metabolic Functions ◽  
A Genome ◽  
Genome Scale

Bacterial lineages that establish obligate symbiotic associations with insect hosts are known to possess highly reduced genomes with streamlined metabolic functions that are commonly focused on amino acid and vitamin synthesis. We constructed a genome-scale metabolic model of the whitefly bacterial endosymbiont Candidatus Portiera aleyrodidarum to study the energy production capabilities using stoichiometric analysis. Strikingly, the results suggest that the energetic metabolism of the bacterial endosymbiont relies on the use of pathways related to the synthesis of amino acids and carotenoids. A deeper insight showed that the ATP production via carotenoid synthesis may also have a potential role in the regulation of amino acid production. The coupling of energy production to anabolism suggest that minimization of metabolic networks as a consequence of genome size reduction does not necessarily limit the biosynthetic potential of obligate endosymbionts.

scholarly journals Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 88
Author(s):  
Dorothy Pei Shan Chang ◽  
Xue Li Guan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lipid Metabolism ◽  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Current Knowledge ◽  
Mycobacterial Infection ◽  
Central Carbon Metabolism ◽  
Metabolic Versatility ◽  
Response To Stress

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a highly successful intracellular pathogen with the ability to withstand harsh conditions and reside long-term within its host. In the dormant and persistent states, the bacterium tunes its metabolism and is able to resist the actions of antibiotics. One of the main strategies Mtb adopts is through its metabolic versatility—it is able to cometabolize a variety of essential nutrients and direct these nutrients simultaneously to multiple metabolic pathways to facilitate the infection of the host. Mtb further undergo extensive remodeling of its metabolic pathways in response to stress and dormancy. In recent years, advancement in systems biology and its applications have contributed substantially to a more coherent view on the intricate metabolic networks of Mtb. With a more refined appreciation of the roles of metabolism in mycobacterial infection and drug resistance, and the success of drugs targeting metabolism, there is growing interest in further development of anti-TB therapies that target metabolism, including lipid metabolism and oxidative phosphorylation. Here, we will review current knowledge revolving around the versatility of Mtb in remodeling its metabolism during infection and dormancy, with a focus on central carbon metabolism and lipid metabolism.

Fluxes through plant metabolic networks: measurements, predictions, insights and challenges

2014 ◽  
Vol 465 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Nicholas J. Kruger ◽  
R. George Ratcliffe
Keyword(s):  
Metabolic Networks ◽  
Metabolic Flux ◽  
Cell Function ◽  
Kinetic Modelling ◽  
Reducing Power ◽  
Central Carbon Metabolism ◽  
Flux Analysis ◽  
Stable Isotope Labelling ◽  
Balance Analysis ◽  
Power And Energy

Although the flows of material through metabolic networks are central to cell function, they are not easy to measure other than at the level of inputs and outputs. This is particularly true in plant cells, where the network spans multiple subcellular compartments and where the network may function either heterotrophically or photoautotrophically. For many years, kinetic modelling of pathways provided the only method for describing the operation of fragments of the network. However, more recently, it has become possible to map the fluxes in central carbon metabolism using the stable isotope labelling techniques of metabolic flux analysis (MFA), and to predict intracellular fluxes using constraints-based modelling procedures such as flux balance analysis (FBA). These approaches were originally developed for the analysis of microbial metabolism, but over the last decade, they have been adapted for the more demanding analysis of plant metabolic networks. Here, the principal features of MFA and FBA as applied to plants are outlined, followed by a discussion of the insights that have been gained into plant metabolic networks through the application of these time-consuming and non-trivial methods. The discussion focuses on how a system-wide view of plant metabolism has increased our understanding of network structure, metabolic perturbations and the provision of reducing power and energy for cell function. Current methodological challenges that limit the scope of plant MFA are discussed and particular emphasis is placed on the importance of developing methods for cell-specific MFA.

scholarly journals Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jared S. Mackenzie ◽  
Dirk A. Lamprecht ◽  
Rukaya Asmal ◽  
John H. Adamson ◽  
Khushboo Borah ◽  
...  
Keyword(s):  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Metabolic Flux ◽  
Tca Cycle ◽  
Central Carbon Metabolism ◽  
Atp Production ◽  
Isotopomer Analysis ◽  
Metabolic Mechanism ◽  
Substantial Interest ◽  
Insight Into

AbstractThe approval of bedaquiline (BDQ) for the treatment of tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death in Mycobacterium tuberculosis (Mtb). Using 13C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon metabolism to induce a metabolically vulnerable state susceptible to genetic disruption of glycolysis and gluconeogenesis. Metabolic flux profiles indicate that BDQ-treated Mtb is dependent on glycolysis for ATP production, operates a bifurcated TCA cycle by increasing flux through the glyoxylate shunt, and requires enzymes of the anaplerotic node and methylcitrate cycle. Targeting oxidative phosphorylation (OXPHOS) with BDQ and simultaneously inhibiting substrate level phosphorylation via genetic disruption of glycolysis leads to rapid sterilization. Our findings provide insight into the metabolic mechanism of BDQ-induced cell death and establish a paradigm for the development of combination therapies that target OXPHOS and glycolysis.

Role of lipid metabolism and systemic inflammation in the development of atherosclerosis in animal models

2021 ◽  
Vol 29 (1) ◽  
pp. 134-146
Author(s):  
Stanislav N. Kotlyarov ◽  
Anna A. Kotlyarova
Keyword(s):  
Immune Response ◽  
Lipid Metabolism ◽  
Amino Acid ◽  
Animal Models ◽  
Systemic Inflammation ◽  
Amino Acid Sequences ◽  
Innate Immune ◽  
Adequate Model ◽  
Study Results ◽  
Species Specific

Systemic inflammation makes a significant contribution to the pathogenesis of atherosclerosis and has been the subject of numerous studies. Works aiming to analyze the mechanisms of atherosclerosis development often include experiments on animals. A primary task of such research is the characterization, justification, and selection of an adequate model. Aim. To evaluate the peculiarities of lipid metabolism and systemic inflammation in chronic obstructive pulmonary disease (COPD) in the development of atherosclerosis in animal models. Materials and Methods. Analyses of cross-links between species-specific peculiarities of lipid metabolism and the immune response, as well as a bioinformatic analysis of differences in Toll-like receptor 4 (TLR4) in mice, rats, and rabbits in comparison with its human homolog, were carried out. A search for and analysis of the amino acid sequences of human, mouse, rat, and rabbit TLR4 was performed in the International database GenBank of National Center of Biotechnical Information and in The Universal Protein Resource (UniProt) database. Multiple alignments of the TLR4 amino acid sequences were implemented in the Clustal Omega program, version 1.2.4. Reconstruction and visualization of molecular phylogenetic trees were performed using the MEGA7 program according to the Neighbor-Joining and Maximum Parsimony methods. Results. Species-specific differences of the peculiarities of lipid metabolism and the innate immune response in humans, mice, and rabbits were shown that must be taken into account in analyses of study results. Conclusion.Disorders in lipid metabolism and systemic inflammation mediated by the innate immune system participating in the pathogenesis of atherosclerosis in COPD possess species-specific differences that should be taken into account in analyses of study results.

Bioluminescent proteins prediction with voting strategy.

2020 ◽  
Vol 15 ◽  
Author(s):  
Shulin Zhao ◽  
Ying Ju ◽  
Xiucai Ye ◽  
Jun Zhang ◽  
Shuguang Han
Keyword(s):  
Amino Acid ◽  
Model Building ◽  
Prediction Method ◽  
Pair Composition ◽  
Proposed Model ◽  
Counting Rules ◽  
Significant Phenomenon ◽  
Voting Strategy ◽  
Improved Accuracy ◽  
Selection Of

Background: Bioluminescence is a unique and significant phenomenon in nature. Bioluminescence is important for the lifecycle of some organisms and is valuable in biomedical research, including for gene expression analysis and bioluminescence imaging technology.In recent years, researchers have identified a number of methods for predicting bioluminescent proteins (BLPs), which have increased in accuracy, but could be further improved. Method: In this paper, we propose a new bioluminescent proteins prediction method based on a voting algorithm. We used four methods of feature extraction based on the amino acid sequence. We extracted 314 dimensional features in total from amino acid composition, physicochemical properties and k-spacer amino acid pair composition. In order to obtain the highest MCC value to establish the optimal prediction model, then used a voting algorithm to build the model.To create the best performing model, we discuss the selection of base classifiers and vote counting rules. Results: Our proposed model achieved 93.4% accuracy, 93.4% sensitivity and 91.7% specificity in the test set, which was better than any other method. We also improved a previous prediction of bioluminescent proteins in three lineages using our model building method, resulting in greatly improved accuracy.

scholarly journals Sequence Comparison of Vaginolysin from Different Gardnerella Species

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 86
Author(s):  
Erin M. Garcia ◽  
Myrna G. Serrano ◽  
Laahirie Edupuganti ◽  
David J. Edwards ◽  
Gregory A. Buck ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Distinct Species ◽  
Vaginal Swab ◽  
Metagenomic Data ◽  
Gardnerella Vaginalis ◽  
Vaginal Epithelial Cells ◽  
Species Specific

Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.

scholarly journals Kog1/Raptor mediates metabolic rewiring during nutrient limitation by controlling SNF1/AMPK activity

2021 ◽  
Vol 7 (16) ◽  
pp. eabe5544
Author(s):  
Zeenat Rashida ◽  
Rajalakshmi Srinivasan ◽  
Meghana Cyanam ◽  
Sunil Laxman
Keyword(s):  
Amino Acid ◽  
Nutrient Limitation ◽  
Carbon Flux ◽  
Metabolic Flux ◽  
Carbon Allocation ◽  
Carbon Utilization ◽  
Acid Biosynthesis ◽  
Control Growth ◽  
Ampk Activity ◽  
Delayed Growth

In changing environments, cells modulate resource budgeting through distinct metabolic routes to control growth. Accordingly, the TORC1 and SNF1/AMPK pathways operate contrastingly in nutrient replete or limited environments to maintain homeostasis. The functions of TORC1 under glucose and amino acid limitation are relatively unknown. We identified a modified form of the yeast TORC1 component Kog1/Raptor, which exhibits delayed growth exclusively during glucose and amino acid limitations. Using this, we found a necessary function for Kog1 in these conditions where TORC1 kinase activity is undetectable. Metabolic flux and transcriptome analysis revealed that Kog1 controls SNF1-dependent carbon flux apportioning between glutamate/amino acid biosynthesis and gluconeogenesis. Kog1 regulates SNF1/AMPK activity and outputs and mediates a rapamycin-independent activation of the SNF1 targets Mig1 and Cat8. This enables effective glucose derepression, gluconeogenesis activation, and carbon allocation through different pathways. Therefore, Kog1 centrally regulates metabolic homeostasis and carbon utilization during nutrient limitation by managing SNF1 activity.

scholarly journals The identification of novel immunogenic antigens as potential Shigella vaccine components

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruklanthi de Alwis ◽  
Li Liang ◽  
Omid Taghavian ◽  
Emma Werner ◽  
Hao Chung The ◽  
...  
Keyword(s):  
Core Genome ◽  
Genomic Analysis ◽  
Carrier Proteins ◽  
Vaccine Candidates ◽  
Vaccine Antigens ◽  
Bactericidal Antibody ◽  
In Vivo Testing ◽  
Species Specific ◽  
Selection Of

Abstract Background Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen. Methods Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections. Results Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody. Conclusions These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.

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