scholarly journals Membrane permeability differentiation at the lipid divide

2021 ◽  
Author(s):  
Urszula Lapinska ◽  
Zehra Kahveci ◽  
Nicholas Irwin ◽  
David Milner ◽  
Alyson E S Santoro ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Metabolic Networks ◽  
Gene Families ◽  
Tree Of Life ◽  
Cellular Systems ◽  
Head Group ◽  
Systematic Analysis ◽  
Bacterial Membranes ◽  
Permeability Function ◽  
Direct Measurements

One of the deepest branches in the tree of life separates the Archaea from the Bacteria. These prokaryotic groups have distinct cellular systems including fundamentally different phospholipid membrane bilayers. This dichotomy has been termed the lipid divide and is assumed to bestow different biophysical and biochemical characteristics on each cell type. Classic experiments suggest that bacterial membranes are more permeable, yet systematic analysis based on direct measurements is absent. Here we develop a new approach for assessing the membrane permeability of cell-sized unilamellar vesicles, consisting of an aqueous medium enclosed by a single lipid bilayer. Comparing the permeability of twenty metabolites demonstrates that archaeal-type membranes are permeable to a range of compounds useful for core metabolic networks, including amino acids, sugars, and nucleobases. Surprisingly, permeability is much lower in bacterial-type membranes, in contradiction to current orthodoxy. We then show that archaeal permeability traits are specifically linked to both the methyl branches present on the archaeal phospholipid tails and the ether link between the tails and the head group. To explore this result further, we compare the abundance of transporter-encoding families present on genomes sampled from across the prokaryotic tree of life. Interestingly, archaea have a reduced repertoire of transporter gene families, consistent with an increased dependency on membrane permeation for a subset of metabolites. Taken together, these results demonstrate that the lipid divide demarcates a clear difference in permeability function with implications for understanding some of the earliest transitions in cell and protocell evolution.

Interactions of the Antimicrobial Peptide Maculatin 1.1 and Analogues with Phospholipid Bilayers

2011 ◽  
Vol 64 (6) ◽  
pp. 798 ◽  
Author(s):  
David I. Fernandez ◽  
Marc-Antoine Sani ◽  
Frances Separovic
Keyword(s):  
Antimicrobial Peptide ◽  
Solid State Nmr ◽  
Acyl Chain ◽  
Head Group ◽  
Group Interactions ◽  
Bacterial Membranes ◽  
Helical Content ◽  
Lipid System ◽  
Acyl Chains ◽  
Mixed Bilayer

The interactions of the antimicrobial peptide, maculatin 1.1 (GLFGVLAKVAAHVVPAIAEHF-NH2) and two analogues, with model phospholipid membranes have been studied using solid-state NMR and circular dichroism spectroscopy. Maculatin 1.1 and the P15G and P15A analogues displayed minimal secondary structure in water, but with zwitterionic dimyristoylphosphatidylcholine (DMPC) vesicles displayed a significant increase in α-helical content. In mixed phospholipid vesicles of DMPC and anionic dimyristoylphosphatidylglycerol (DMPG), each peptide was highly structured with ~80% α-helical content. In DMPC vesicles, the native peptide displayed moderate head group interaction and significant perturbation of the lipid acyl chains. In DMPC/DMPG vesicles, maculatin 1.1 promoted formation of a DMPG-enriched phase and moderately increased disorder towards acyl chain ends of DMPC in the mixed bilayer. Both analogues showed reduced phospholipid head group interactions with DMPC but displayed significant interactions with the mixed lipid system. These effects support the preferential activity of these antimicrobial peptides for bacterial membranes.

scholarly journals Genome-scale reconstructions to assess metabolic phylogeny and organism clustering

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240953
Author(s):  
Christian Schulz ◽  
Eivind Almaas
Keyword(s):  
Phylogenetic Trees ◽  
Metabolic Networks ◽  
Sulfur Metabolism ◽  
Phylogenetic Analyses ◽  
Tree Of Life ◽  
Significant Heterogeneity ◽  
Metabolic Reaction ◽  
High Quality ◽  
Conserved Genes ◽  
Genome Scale

Approaches for systematizing information of relatedness between organisms is important in biology. Phylogenetic analyses based on sets of highly conserved genes are currently the basis for the Tree of Life. Genome-scale metabolic reconstructions contain high-quality information regarding the metabolic capability of an organism and are typically restricted to metabolically active enzyme-encoding genes. While there are many tools available to generate draft reconstructions, expert-level knowledge is still required to generate and manually curate high-quality genome-scale metabolic models and to fill gaps in their reaction networks. Here, we use the tool AutoKEGGRec to construct 975 genome-scale metabolic draft reconstructions encoded in the KEGG database without further curation. The organisms are selected across all three domains, and their metabolic networks serve as basis for generating phylogenetic trees. We find that using all reactions encoded, these metabolism-based comparisons give rise to a phylogenetic tree with close similarity to the Tree of Life. While this tree is quite robust to reasonable levels of noise in the metabolic reaction content of an organism, we find a significant heterogeneity in how much noise an organism may tolerate before it is incorrectly placed in the tree. Furthermore, by using the protein sequences for particular metabolic functions and pathway sets, such as central carbon-, nitrogen-, and sulfur-metabolism, as basis for the organism comparisons, we generate highly specific phylogenetic trees. We believe the generation of phylogenetic trees based on metabolic reaction content, in particular when focused on specific functions and pathways, could aid the identification of functionally important metabolic enzymes and be of value for genome-scale metabolic modellers and enzyme-engineers.

scholarly journals Elaboration of the corticosteroid synthesis pathway in primates through a multi-step enzyme

2019 ◽  
Author(s):  
Carrie F. Olson-Manning
Keyword(s):  
Cytochrome P450 ◽  
Gene Duplication ◽  
Metabolic Networks ◽  
Cellular Systems ◽  
Potential Outcomes ◽  
Enzymatic Reactions ◽  
Ancestral State ◽  
State Reconstruction ◽  
Specific Regulation

AbstractMetabolic networks are complex cellular systems dependent on the interactions among, and regulation of, the enzymes in the network. However, the mechanisms that lead to the expansion of networks are not well understood. While gene duplication is a major driver of the expansion and functional evolution of metabolic networks, the effect and fate of retained duplicates in a network is poorly understood. Here, I study the evolution of an enzyme family that performs multiple subsequent enzymatic reactions in the corticosteroid pathway in primates to illuminate the mechanisms that shape network components following duplication. The products of the pathway (aldosterone, corticosterone, and cortisol) are steroid hormones that regulate metabolism and stress in tetrapods. These steroids are synthesized by a multi-step enzyme Cytochrome P450 11B (CYP11B) that performs subsequent steps on different carbon atoms of the steroid derivatives. Through ancestral state reconstruction and in vitro characterization, I find the ancestor of the CYP11B1 and CYP11B2 paralogs (in primates) had moderate ability to synthesize cortisol and aldosterone. Following duplication in the primate lineage the CYP11B1 homolog specialized on the production of cortisol while its paralog, CYP11B2, maintained its ability to perform multiple subsequent steps as in the ancestral pathway. Unlike CYP11B1, CYP11B2 could not specialize on the production of aldosterone because it is constrained to perform earlier steps in the corticosteroid synthesis pathway to achieve the final product aldosterone. These results suggest that pathway context, along with tissue-specific regulation, both play a role in shaping potential outcomes of metabolic network elaboration.

scholarly journals Gene Families, Epistasis and the Amino Acid Preferences of Protein Homologs

2019 ◽  
Vol 15 ◽  
pp. 117693431987048
Author(s):  
Evandro Ferrada
Keyword(s):  
Amino Acid ◽  
Genetic Background ◽  
Sequence Divergence ◽  
Gene Families ◽  
Structure And Function ◽  
Sequence Evolution ◽  
Systematic Analysis ◽  
Fitness Effects ◽  
Computational Work ◽  
And Function

In order to preserve structure and function, proteins tend to preferentially conserve amino acids at particular sites along the sequence. Because mutations can affect structure and function, the question arises whether the preference of a protein site for a particular amino acid varies between protein homologs, and to what extent that variation depends on sequence divergence. Answering these questions can help in the development of models of sequence evolution, as well as provide insights on the dependence of the fitness effects of mutations on the genetic background of sequences, a phenomenon known as epistasis. Here, I comment on recent computational work providing a systematic analysis of the extent to which the amino acid preferences of proteins depend on the background mutations of protein homologs.

scholarly journals Antibacterial Effect of Chitosan–Gold Nanoparticles and Computational Modeling of the Interaction between Chitosan and a Lipid Bilayer Model

Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2340
Author(s):  
M. G. Fuster ◽  
M. G. Montalbán ◽  
G. Carissimi ◽  
B. Lima ◽  
G. E. Feresin ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Simulation Model ◽  
Pathogenic Bacteria ◽  
Antibacterial Effect ◽  
Resistance Mechanisms ◽  
Target Point ◽  
Systematic Analysis ◽  
Bacterial Membranes ◽  
Synthesis Parameters ◽  
Cell Wall Disruption

Pathogenic bacteria have the ability to develop antibiotic resistance mechanisms. Their action consists mainly in the production of bacterial enzymes that inactivate antibiotics or the appearance of modifications that prevent the arrival of the drug at the target point or the alteration of the target point itself, becoming a growing problem for health systems. Chitosan–gold nanoparticles (Cs-AuNPs) have been shown as effective bactericidal materials avoiding damage to human cells. In this work, Cs-AuNPs were synthesized using chitosan as the reducing agent, and a systematic analysis of the influence of the synthesis parameters on the size and zeta potential of the Cs-AuNPs and their UV-vis spectra was carried out. We used a simulation model to characterize the interaction of chitosan with bacterial membranes, using a symmetric charged bilayer and two different chitosan models with different degrees of the chitosan amine protonation as a function of pH, with the aim to elucidate the antibacterial mechanism involving the cell wall disruption. The Cs-AuNP antibacterial activity was evaluated to check the simulation model.

scholarly journals Elaboration of the Corticosteroid Synthesis Pathway in Primates through a Multistep Enzyme

2020 ◽  
Vol 37 (8) ◽  
pp. 2257-2267
Author(s):  
Carrie F Olson-Manning
Keyword(s):  
Steroid Hormones ◽  
Metabolic Networks ◽  
Cellular Systems ◽  
Potential Outcomes ◽  
Enzymatic Reactions ◽  
Ancestral State ◽  
Biochemical Pathways ◽  
In Vitro Characterization ◽  
Specific Regulation

Abstract Metabolic networks are complex cellular systems dependent on the interactions among, and regulation of, the enzymes in the network. Although there is great diversity of types of enzymes that make up metabolic networks, the models meant to understand the possible evolutionary outcomes following duplication neglect specifics about the enzyme, pathway context, and cellular constraints. To illuminate the mechanisms that shape the evolution of biochemical pathways, I functionally characterize the consequences of gene duplication of an enzyme family that performs multiple subsequent enzymatic reactions (a multistep enzyme) in the corticosteroid pathway in primates. The products of the corticosteroid pathway (aldosterone and cortisol) are steroid hormones that regulate metabolism and stress response in tetrapods. These steroid hormones are synthesized by a multistep enzyme Cytochrome P450 11B (CYP11B) that performs subsequent steps on different carbon atoms of the steroid derivatives. Through ancestral state reconstruction and in vitro characterization, I find that the primate ancestor of the CYP11B1 and CYP11B2 paralogs had moderate ability to synthesize both cortisol and aldosterone. Following duplication in Old World primates, the CYP11B1 homolog specialized on the production of cortisol, whereas its paralog, CYP11B2, maintained its ability to perform multiple subsequent steps as in the ancestral pathway. Unlike CYP11B1, CYP11B2 could not specialize on the production of aldosterone because it is constrained to perform earlier steps in the corticosteroid synthesis pathway to achieve the final product aldosterone. These results suggest that enzyme function, pathway context, along with tissue-specific regulation, both play a role in shaping potential outcomes of metabolic network elaboration.

scholarly journals Systematic Analysis of the DNA Methylase and Demethylase Gene Families in Rapeseed (Brassica napus L.) and Their Expression Variations After Salt and Heat stresses

2020 ◽  
Vol 21 (3) ◽  
pp. 953 ◽  
Author(s):  
Shihang Fan ◽  
Hongfang Liu ◽  
Jing Liu ◽  
Wei Hua ◽  
Shouming Xu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brassica Napus ◽  
Stress Responses ◽  
Methylation Status ◽  
Functional Characterization ◽  
Gene Families ◽  
Brassica Napus L ◽  
Systematic Analysis ◽  
Dna Methylase ◽  
Dna Demethylase

DNA methylation is a process through which methyl groups are added to the DNA molecule, thereby modifying the activity of a DNA segment without changing the sequence. Increasing evidence has shown that DNA methylation is involved in various aspects of plant growth and development via a number of key processes including genomic imprinting and repression of transposable elements. DNA methylase and demethylase are two crucial enzymes that play significant roles in dynamically maintaining genome DNA methylation status in plants. In this work, 22 DNA methylase genes and six DNA demethylase genes were identified in rapeseed (Brassica napus L.) genome. These DNA methylase and DNA demethylase genes can be classified into four (BnaCMTs, BnaMET1s, BnaDRMs and BnaDNMT2s) and three (BnaDMEs, BnaDML3s and BnaROS1s) subfamilies, respectively. Further analysis of gene structure and conserved domains showed that each sub-class is highly conserved between rapeseed and Arabidopsis. Expression analysis conducted by RNA-seq as well as qRT-PCR suggested that these DNA methylation/demethylation-related genes may be involved in the heat/salt stress responses in rapeseed. Taken together, our findings may provide valuable information for future functional characterization of these two types of epigenetic regulatory enzymes in polyploid species such as rapeseed, as well as for analyzing their evolutionary relationships within the plant kingdom.

Membrane permeability of isolated lung cells to nonelectrolytes at different temperatures

1982 ◽  
Vol 243 (5) ◽  
pp. C285-C292 ◽  
Author(s):  
R. A. Garrick ◽  
F. P. Chinard
Keyword(s):  
Membrane Permeability ◽  
Tritiated Water ◽  
Cellular Systems ◽  
Lung Cells ◽  
Cell Preparation ◽  
Rabbit Lung ◽  
Novikoff Hepatoma ◽  
Permeability Coefficients ◽  
Diffusional Permeability ◽  
Isolated Lung

Membrane permeability coefficients (P0) of rabbit lung cells consisting primarily of alveolar epithelial and endothelial cells and of alveolar macrophages from dog lungs were determined for tritiated water, n-[14C]alcohols, and [14C]antipyrine over the temperature range 10 to 37 degrees C with the series-parallel pathway model. In the mixed cell preparation both the diffusional permeability to water (755 X 10(-5) cm.s-1 at 37 degrees C) and the response to temperature change (apparent activation energy, Ea, 10 kcal.mol-1) are greater than the corresponding values in the macrophages (110 X 10(-5) cm.s-1 and 4.8 kcal.mol-1, respectively). The permeability coefficients for the small alcohols (C1-C3) are similar and considerably higher than for water in both cellular preparations. The values of the permeability coefficients and the temperature dependence for antipyrine and the larger alcohols in the mixed lung cells differ from the values obtained in the macrophages. Comparison of our results with those obtained in erythrocytes and Novikoff hepatoma cells demonstrates the differences in water permeability in each cell preparation and the similarity in permeation for the more lipophilic solutes in the cell preparations. These differences may be important in the comparison of results obtained in isolated cellular systems and in intact tissues and organs.

scholarly journals Modeling the Differences in Biochemical Capabilities ofPseudomonasSpecies by Flux Balance Analysis: How Good Are Genome-Scale Metabolic Networks at Predicting the Differences?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Parizad Babaei ◽  
Tahereh Ghasemi-Kahrizsangi ◽  
Sayed-Amir Marashi
Keyword(s):  
In Silico ◽  
Metabolic Networks ◽  
Closely Related Species ◽  
Systematic Analysis ◽  
Reconstruction Process ◽  
Flux Balance ◽  
Wide Range ◽  
Balance Analysis ◽  
Metabolic Models ◽  
Genome Scale

To date, several genome-scale metabolic networks have been reconstructed. These models cover a wide range of organisms, from bacteria to human. Such models have provided us with a framework for systematic analysis of metabolism. However, little effort has been put towards comparing biochemical capabilities of closely related species using their metabolic models. The accuracy of a model is highly dependent on the reconstruction process, as some errors may be included in the model during reconstruction. In this study, we investigated the ability of threePseudomonasmetabolic models to predict the biochemical differences, namely, iMO1086, iJP962, and iSB1139, which are related toP. aeruginosaPAO1,P. putidaKT2440, andP. fluorescensSBW25, respectively. We did a comprehensive literature search for previous works containing biochemically distinguishable traits over these species. Amongst more than 1700 articles, we chose a subset of them which included experimental results suitable forin silicosimulation. By simulating the conditions provided in the actual biological experiment, we performed case-dependent tests to compare thein silicoresults to the biological ones. We found out that iMO1086 and iJP962 were able to predict the experimental data and were much more accurate than iSB1139.

scholarly journals Systematic Analysis of Functionally Related Gene Clusters in the Opportunistic Pathogen, Candida albicans

2021 ◽  
Vol 9 (2) ◽  
pp. 276
Author(s):  
Sarah Asfare ◽  
Reem Eldabagh ◽  
Khizar Siddiqui ◽  
Bharvi Patel ◽  
Diellza Kaba ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Gene Families ◽  
Gene Clusters ◽  
Opportunistic Pathogen ◽  
Systematic Analysis ◽  
Genomic Arrangement ◽  
A Genome ◽  
Opportunistic Human Pathogen ◽  
Organismal Development

The proper balance of gene expression is essential for cellular health, organismal development, and maintaining homeostasis. In response to complex internal and external signals, the cell needs to modulate gene expression to maintain proteostasis and establish cellular identity within its niche. On a genome level, single-celled prokaryotic microbes display clustering of co-expressed genes that are regulated as a polycistronic RNA. This phenomenon is largely absent from eukaryotic microbes, although there is extensive clustering of co-expressed genes as functional pairs spread throughout the genome in Saccharomyces cerevisiae. While initial analysis demonstrated conservation of clustering in divergent fungal lineages, a comprehensive analysis has yet to be performed. Here we report on the prevalence, conservation, and significance of the functional clustering of co-regulated genes within the opportunistic human pathogen, Candida albicans. Our analysis reveals that there is extensive clustering within this organism—although the identity of the gene pairs is unique compared with those found in S. cerevisiae—indicating that this genomic arrangement evolved after these microbes diverged evolutionarily, rather than being the result of an ancestral arrangement. We report a clustered arrangement in gene families that participate in diverse molecular functions and are not the result of a divergent orientation with a shared promoter. This arrangement coordinates the transcription of the clustered genes to their neighboring genes, with the clusters congregating to genomic loci that are conducive to transcriptional regulation at a distance.

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