scholarly journals Computational Modeling and Evolutionary Implications of Biochemical Reactions in Bacterial Microcompartments

2021 ◽  
Author(s):  
Clair A. Huffine ◽  
Lucas C. Wheeler ◽  
Boswell Wing ◽  
Jeffrey Carlyle Cameron
Keyword(s):  
Computational Modeling ◽  
Substrate Concentration ◽  
Reaction Rates ◽  
Biochemical Reactions ◽  
Ph Gradients ◽  
Bacterial Phyla ◽  
Bacterial Microcompartments ◽  
Oxygen Sensitive ◽  
Systematic Understanding ◽  
Protein Shell

Bacterial microcompartments (BMCs) are protein-encapsulated compartments found across at least 23 bacterial phyla. BMCs contain a variety of metabolic processes that share the commonality of toxic or volatile intermediates, oxygen-sensitive enzymes and cofactors, or increased substrate concentration for magnified reaction rates. These compartmentalized reactions have been computationally modeled to explore the encapsulated dynamics, ask evolutionary-based questions, and develop a more systematic understanding required for the engineering of novel BMCs. Many crucial aspects of these systems remain unknown or unmeasured, such as substrate permeabilities across the protein shell, feasibility of pH gradients, and transport rates of associated substrates into the cell. This review explores existing BMC models, dominated in the literature by cyanobacterial carboxysomes, and highlights potentially important areas for exploration.

Clues to the function of bacterial microcompartments from ancillary genes

2021 ◽  
Author(s):  
Henning Kirst ◽  
Cheryl A. Kerfeld
Keyword(s):  
Metabolic Pathways ◽  
Transmembrane Proteins ◽  
Transcriptional Regulators ◽  
Building Blocks ◽  
Data Set ◽  
Bacterial Phyla ◽  
Bacterial Microcompartments ◽  
Shell Proteins ◽  
Regulation Mechanisms ◽  
Protein Shell

Bacterial microcompartments (BMCs) are prokaryotic organelles. Their bounding membrane is a selectively permeable protein shell, encapsulating enzymes of specialized metabolic pathways. While the function of a BMC is dictated by the encapsulated enzymes which vary with the type of the BMC, the shell is formed by conserved protein building blocks. The genes necessary to form a BMC are typically organized in a locus; they encode the shell proteins, encapsulated enzymes as well as ancillary proteins that integrate the BMC function into the cell's metabolism. Among these are transcriptional regulators which usually found at the beginning or end of a locus, and transmembrane proteins that presumably function to conduct the BMC substrate into the cell. Here, we describe the types of transcriptional regulators and permeases found in association with BMC loci, using a recently collected data set of more than 7000 BMC loci distributed over 45 bacterial phyla, including newly discovered BMC loci. We summarize the known BMC regulation mechanisms, and highlight how much remains to be uncovered. We also show how analysis of these ancillary proteins can inform hypotheses about BMC function; by examining the ligand-binding domain of the regulator and the transporter, we propose that nucleotides are the likely substrate for an enigmatic uncharacterized BMC of unknown function.

scholarly journals A Survey of Bacterial Microcompartment Distribution in the Human Microbiome

2021 ◽  
Vol 12 ◽  
Author(s):  
Kunica Asija ◽  
Markus Sutter ◽  
Cheryl A. Kerfeld
Keyword(s):  
Sequence Data ◽  
Human Microbiome ◽  
Metabolic Potential ◽  
Bacterial Phyla ◽  
Bacterial Microcompartments ◽  
Bacterial Microcompartment ◽  
Different Types ◽  
Shell Proteins ◽  
Enzymatic Pathways ◽  
Protein Shell

Bacterial microcompartments (BMCs) are protein-based organelles that expand the metabolic potential of many bacteria by sequestering segments of enzymatic pathways in a selectively permeable protein shell. Sixty-eight different types/subtypes of BMCs have been bioinformatically identified based on the encapsulated enzymes and shell proteins encoded in genomic loci. BMCs are found across bacterial phyla. The organisms that contain them, rather than strictly correlating with specific lineages, tend to reflect the metabolic landscape of the environmental niches they occupy. From our recent comprehensive bioinformatic survey of BMCs found in genome sequence data, we find many in members of the human microbiome. Here we survey the distribution of BMCs in the different biotopes of the human body. Given their amenability to be horizontally transferred and bioengineered they hold promise as metabolic modules that could be used to probiotically alter microbiomes or treat dysbiosis.

scholarly journals Impact of flow velocity on biochemical processes – a laboratory experiment

2014 ◽  
Vol 11 (8) ◽  
pp. 9829-9862 ◽  
Author(s):  
A. Boisson ◽  
D. Roubinet ◽  
L. Aquilina ◽  
O. Bour ◽  
P. Davy
Keyword(s):  
Laboratory Experiment ◽  
Flow Velocity ◽  
Chemical Properties ◽  
Reaction Rates ◽  
Natural Environments ◽  
Biochemical Reactions ◽  
Mobile Electron ◽  
Immobile Phase ◽  
Biofilm Development ◽  
The Impact

Abstract. Understanding and predicting hydraulic and chemical properties of natural environments are current crucial challenges. It requires considering hydraulic, chemical and biological processes and evaluating how hydrodynamic properties impact on biochemical reactions. In this context, an original laboratory experiment to study the impact of flow velocity on biochemical reactions along a one-dimensional flow streamline has been developed. Based on the example of nitrate reduction, nitrate-rich water passes through plastic tubes at several flow velocities (from 6.2 to 35 mm min−1), while nitrate concentration at the tube outlet is monitored for more than 500 h. This experimental setup allows assessing the biologically controlled reaction between a mobile electron acceptor (nitrate) and an electron donor (carbon) coming from an immobile phase (tube) that produces carbon during its degradation by microorganisms. It results in observing a dynamic of the nitrate transformation associated with biofilm development which is flow-velocity dependent. It is proposed that the main behaviors of the reaction rates are related to phases of biofilm development through a simple analytical model including assimilation. Experiment results and their interpretation demonstrate a significant impact of flow velocity on reaction performance and stability and highlight the relevance of dynamic experiments over static experiments for understanding biogeochemical processes.

scholarly journals Glycyl Radical Enzyme-Associated Microcompartments: Redox-Replete Bacterial Organelles

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bryan Ferlez ◽  
Markus Sutter ◽  
Cheryl A. Kerfeld
Keyword(s):  
Substrate Specificity ◽  
Pathogenic Bacteria ◽  
External Source ◽  
Redox Proteins ◽  
Physiological Importance ◽  
Bacterial Microcompartments ◽  
Glycyl Radical ◽  
Self Assembling ◽  
Glycyl Radical Enzyme ◽  
Protein Shell

ABSTRACTAn increasing number of microbes are being identified that organize catabolic pathways within self-assembling proteinaceous structures known as bacterial microcompartments (BMCs). Most BMCs are characterized by their singular substrate specificity and commonly employ B12-dependent radical mechanisms. In contrast, a less-well-known BMC type utilizes the B12-independent radical chemistry of glycyl radical enzymes (GREs). Unlike B12-dependent enzymes, GREs require an activating enzyme (AE) as well as an external source of electrons to generate an adenosyl radical and form their catalytic glycyl radical. Organisms encoding these glycyl radical enzyme-associated microcompartments (GRMs) confront the challenge of coordinating the activation and maintenance of their GREs with the assembly of a multienzyme core that is encapsulated in a protein shell. The GRMs appear to enlist redox proteins to either generate reductants internally or facilitate the transfer of electrons from the cytosol across the shell. Despite this relative complexity, GRMs are one of the most widespread types of BMC, with distinct subtypes to catabolize different substrates. Moreover, they are encoded by many prominent gut-associated and pathogenic bacteria. In this review, we will focus on the diversity, function, and physiological importance of GRMs, with particular attention given to their associated and enigmatic redox proteins.

Experimental determination and computational modeling of threshold reaction rates in 0.8 GeV proton-irradiated lead target

Atomic Energy ◽  
2009 ◽  
Vol 107 (1) ◽  
pp. 48-59 ◽  
Author(s):  
Yu. E. Titarenko ◽  
V. F. Batyaev ◽  
A. Yu. Titarenko ◽  
V. M. Zhivun ◽  
K. V. Pavlov ◽  
...  
Keyword(s):  
Computational Modeling ◽  
Experimental Determination ◽  
Reaction Rates ◽  
Lead Target ◽  
Threshold Reaction

scholarly journals The N Terminus of the PduB Protein Binds the Protein Shell of the Pdu Microcompartment to Its Enzymatic Core

2017 ◽  
Vol 199 (8) ◽  
Author(s):  
Brent P. Lehman ◽  
Chiranjit Chowdhury ◽  
Thomas A. Bobik
Keyword(s):  
Amino Acids ◽  
Protein Complexes ◽  
Critical Role ◽  
Chemical Production ◽  
Protein Subunits ◽  
Bacterial Microcompartments ◽  
Shell Protein ◽  
N Terminus ◽  
Complex Protein ◽  
Protein Shell

ABSTRACT Bacterial microcompartments (MCPs) are extremely large proteinaceous organelles that consist of an enzymatic core encapsulated within a complex protein shell. A key question in MCP biology is the nature of the interactions that guide the assembly of thousands of protein subunits into a well-ordered metabolic compartment. In this report, we show that the N-terminal 37 amino acids of the PduB protein have a critical role in binding the shell of the 1,2-propanediol utilization (Pdu) microcompartment to its enzymatic core. Several mutations were constructed that deleted short regions of the N terminus of PduB. Growth tests indicated that three of these deletions were impaired MCP assembly. Attempts to purify MCPs from these mutants, followed by gel electrophoresis and enzyme assays, indicated that the protein complexes isolated consisted of MCP shells depleted of core enzymes. Electron microscopy substantiated these findings by identifying apparently empty MCP shells but not intact MCPs. Analyses of 13 site-directed mutants indicated that the key region of the N terminus of PduB required for MCP assembly is a putative helix spanning residues 6 to 18. Considering the findings presented here together with prior work, we propose a new model for MCP assembly. IMPORTANCE Bacterial microcompartments consist of metabolic enzymes encapsulated within a protein shell and are widely used to optimize metabolic process. Here, we show that the N-terminal 37 amino acids of the PduB shell protein are essential for assembly of the 1,2-propanediol utilization microcompartment. The results indicate that it plays a key role in binding the outer shell to the enzymatic core. We propose that this interaction might be used to define the relative orientation of the shell with respect to the core. This finding is of fundamental importance to our understanding of microcompartment assembly and may have application to engineering microcompartments as nanobioreactors for chemical production.

scholarly journals Efficient finite-difference method for computing sensitivities of biochemical reactions

2018 ◽  
Vol 474 (2218) ◽  
pp. 20180303 ◽  
Author(s):  
Vo Hong Thanh ◽  
Roberto Zunino ◽  
Corrado Priami
Keyword(s):  
Data Structure ◽  
Finite Difference ◽  
Finite Difference Method ◽  
Difference Method ◽  
Computational Cost ◽  
Reaction Rates ◽  
Biochemical Reactions ◽  
Simulation Step ◽  
Coupling Strategy ◽  
Single Data

Sensitivity analysis of biochemical reactions aims at quantifying the dependence of the reaction dynamics on the reaction rates. The computation of the parameter sensitivities, however, poses many computational challenges when taking stochastic noise into account. This paper proposes a new finite-difference method for efficiently computing sensitivities of biochemical reactions. We employ propensity bounds of reactions to couple the simulation of the nominal and perturbed processes. The exactness of the simulation is preserved by applying the rejection-based mechanism. For each simulation step, the nominal and perturbed processes under our coupling strategy are synchronized and often jump together, increasing their positive correlation and hence reducing the variance of the estimator. The distinctive feature of our approach in comparison with existing coupling approaches is that it only needs to maintain a single data structure storing propensity bounds of reactions during the simulation of the nominal and perturbed processes. Our approach allows to compute sensitivities of many reaction rates simultaneously. Moreover, the data structure does not require to be updated frequently, hence improving the computational cost. This feature is especially useful when applied to large reaction networks. We benchmark our method on biological reaction models to prove its applicability and efficiency.

scholarly journals Reprogramming bacterial protein organelles as a nanoreactor for hydrogen production

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Tianpei Li ◽  
Qiuyao Jiang ◽  
Jiafeng Huang ◽  
Catherine M. Aitchison ◽  
Fang Huang ◽  
...  
Keyword(s):  
Hydrogen Production ◽  
Self Assembly ◽  
Rational Design ◽  
Carbon Fixation ◽  
Catalytic Performance ◽  
Enzyme Activation ◽  
Production Of Hydrogen ◽  
Catalytically Active ◽  
Oxygen Sensitive ◽  
Protein Shell

Abstract Compartmentalization is a ubiquitous building principle in cells, which permits segregation of biological elements and reactions. The carboxysome is a specialized bacterial organelle that encapsulates enzymes into a virus-like protein shell and plays essential roles in photosynthetic carbon fixation. The naturally designed architecture, semi-permeability, and catalytic improvement of carboxysomes have inspired rational design and engineering of new nanomaterials to incorporate desired enzymes into the protein shell for enhanced catalytic performance. Here, we build large, intact carboxysome shells (over 90 nm in diameter) in the industrial microorganism Escherichia coli by expressing a set of carboxysome protein-encoding genes. We develop strategies for enzyme activation, shell self-assembly, and cargo encapsulation to construct a robust nanoreactor that incorporates catalytically active [FeFe]-hydrogenases and functional partners within the empty shell for the production of hydrogen. We show that shell encapsulation and the internal microenvironment of the new catalyst facilitate hydrogen production of the encapsulated oxygen-sensitive hydrogenases. The study provides insights into the assembly and formation of carboxysomes and paves the way for engineering carboxysome shell-based nanoreactors to recruit specific enzymes for diverse catalytic reactions.

scholarly journals A Systems-Level Model Reveals That 1,2-Propanediol Utilization Microcompartments Enhance Pathway Flux Through Intermediate Sequestration

2016 ◽  
Author(s):  
Christopher M. Jakobson ◽  
Marilyn F. Slininger ◽  
Danielle Tullman-Ercek ◽  
Niall M. Mangan
Keyword(s):  
Mathematical Model ◽  
Active Transport ◽  
Substrate Concentration ◽  
Metabolic Pathways ◽  
Salmonella Enterica ◽  
The United States ◽  
Subcellular Organelles ◽  
Bacterial Microcompartments ◽  
Metabolite Concentrations ◽  
Pathway Flux

AbstractThe spatial organization of metabolism is common to all domains of life. Enteric and other bacteria use subcellular organelles known as bacterial microcompartments to spatially organize the metabolism of pathogenicity-relevant carbon sources, such as 1,2-propanediol. The organelles are thought to sequester a private cofactor pool, minimize the effects of toxic intermediates, and enhance flux through the encapsulated metabolic pathways. We develop a mathematical model of the function of the 1,2-propanediol utilization microcompartment of Salmonella enterica and use it to analyze the function of the microcompartment organelles in detail. Our model makes accurate predictions of doubling times based on an optimized compartment shell permeability determined by maximizing metabolic flux in the model. The compartments function primarily to decouple cytosolic intermediate concentrations from the concentrations in the microcompartment, allowing significant enhancement in pathway flux by the generation of large concentration gradients across the microcompartment shell. We find that selective permeability of the microcompartment shell is not absolutely necessary, but is often beneficial in establishing this intermediate-trapping function. Our findings also implicate active transport of the 1,2-propanediol substrate under conditions of low external substrate concentration, and we present a mathematical bound, in terms of external 1,2-proanediol substrate concentration and diffusive rates, on when active transport of the substrate is advantageous. By allowing us to predict experimentally inaccessible aspects of microcompartment function, such as intra-microcompartment metabolite concentrations, our model presents avenues for future research and underscores the importance of carefully considering changes in external metabolite concentrations and other conditions during batch cultures. Our results also suggest that the encapsulation of heterologous pathways in bacterial microcompartments might yield significant benefits for pathway flux, as well as for toxicity mitigation.Author SummaryMany bacterial species, such as Salmonella enterica (responsible for over 1 million illnesses per year in the United States) and Yersinia pestis (the causative agent of bubonic plague), have a suite of unique metabolic capabilities allowing them to proliferate in the hostile environment of the host gut. Bacterial microcompartments are the subcellular organelles that contain the enzymes responsible for these special metabolic pathways. In this study, we use a mathematical model to explore the possible reasons why Salmonella enclose the 1,2-propanediol utilization metabolic pathway within these sophisticated organelle structures. Using our model, we can examine experimentally inaccessible aspects of the system and make predictions to be tested in future experiments. The metabolic benefits that bacteria gain from the microcompartment system may also prove helpful in enhancing bacterial production of fuels, pharmaceuticals, and specialty chemicals.

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