Clues to the function of bacterial microcompartments from ancillary genes

Author(s):  
Henning Kirst ◽  
Cheryl A. Kerfeld

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Kunica Asija ◽  
Markus Sutter ◽  
Cheryl A. Kerfeld

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.


Author(s):  
Jessica M. Ochoa ◽  
Oscar Mijares ◽  
Andrea A. Acosta ◽  
Xavier Escoto ◽  
Nancy Leon-Rivera ◽  
...  

Bacterial microcompartments are large supramolecular structures comprising an outer proteinaceous shell that encapsulates various enzymes in order to optimize metabolic processes. The outer shells of bacterial microcompartments are made of several thousand protein subunits, generally forming hexameric building blocks based on the canonical bacterial microcompartment (BMC) domain. Among the diverse metabolic types of bacterial microcompartments, the structures of those that use glycyl radical enzymes to metabolize choline have not been adequately characterized. Here, six structures of hexameric shell proteins from type I and type II choline-utilization microcompartments are reported. Sequence and structure analysis reveals electrostatic surface properties that are shared between the four types of shell proteins described here.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Markus Sutter ◽  
Matthew R. Melnicki ◽  
Frederik Schulz ◽  
Tanja Woyke ◽  
Cheryl A. Kerfeld

AbstractBacterial microcompartments (BMCs) are organelles that segregate segments of metabolic pathways which are incompatible with surrounding metabolism. BMCs consist of a selectively permeable shell, composed of three types of structurally conserved proteins, together with sequestered enzymes that vary among functionally distinct BMCs. Genes encoding shell proteins are typically clustered with those for the encapsulated enzymes. Here, we report that the number of identifiable BMC loci has increased twenty-fold since the last comprehensive census of 2014, and the number of distinct BMC types has doubled. The new BMC types expand the range of compartmentalized catalysis and suggest that there is more BMC biochemistry yet to be discovered. Our comprehensive catalog of BMCs provides a framework for their identification, correlation with bacterial niche adaptation, experimental characterization, and development of BMC-based nanoarchitectures for biomedical and bioengineering applications.


2021 ◽  
Author(s):  
Markus Sutter ◽  
Matthew R. Melnicki ◽  
Frederik Schulz ◽  
Tanja Woyke ◽  
Cheryl A. Kerfeld

AbstractBacterial microcompartments (BMCs) are organelles that segregate segments of metabolic pathways, which are incompatible with surrounding metabolism. In contrast to their eukaryotic counterparts, the selectively permeable membrane of BMCs, the shell, is composed of protein. While the sequestered enzymes vary among functionally distinct BMCs, the proteins that form diverse BMC shells are structurally homologous; this enables the bioinformatic identification of the organelles by locating genes encoding shell proteins, which are typically proximal to those for the encapsulated enzymes. With recent advances in genome‐resolved metagenomics and the emphasis on “microbial dark matter”, many new genome sequences from diverse and obscure bacterial clades have become available. We find the number of identifiable BMC loci has increased twenty‐fold since the last comprehensive census of 2014. Moreover, the addition of new types we uncovered doubles the number of distinct BMC types known. These expand the range of catalysis encapsulated in BMCs, underscoring that there is dark biochemistry that is compartmentalized in bacterial organelles yet to be discovered through genome sequencing. Our comprehensive catalog of BMCs provides a framework for their identification, correlation with bacterial niche adaptation, and experimental characterization, and broadens the foundation for the development of BMC‐based nanoarchitectures for biomedical and bioengineering applications.


2021 ◽  
Author(s):  
Clair A. Huffine ◽  
Lucas C. Wheeler ◽  
Boswell Wing ◽  
Jeffrey Carlyle Cameron

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.


2010 ◽  
Vol 192 (22) ◽  
pp. 5881-5886 ◽  
Author(s):  
Balaraj B. Menon ◽  
Sabine Heinhorst ◽  
Jessup M. Shively ◽  
Gordon C. Cannon

ABSTRACT Bacterial microcompartments (BMCs) are polyhedral organelles found in an increasingly wide variety of bacterial species. These structures, typified by carboxysomes of cyanobacteria and many chemoautotrophs, function to compartmentalize important reaction sequences of metabolic pathways. Unlike their eukaryotic counterparts, which are surrounded by lipid bilayer membranes, these microbial organelles are bounded by a thin protein shell that is assembled from multiple copies of a few different polypeptides. The main shell proteins form hexamers whose edges interact to create the thin sheets that form the facets of the polyhedral BMCs. Each hexamer contains a central pore hypothesized to mediate flux of metabolites into and out of the organelle. Because several distinctly different metabolic processes are found in the various BMCs studied to date, it has been proposed that a common advantage to packaging these pathways within shell-bound compartments is to optimize the concentration of volatile metabolites in the BMC by maintaining an interior pH that is lower than that of the cytoplasm. We have tested this idea by recombinantly fusing a pH-sensitive green fluorescent protein (GFP) to ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), the major enzyme component inside the carboxysome. Our results suggest that the carboxysomal pH is similar to that of its external environment and that the protein shell does not constitute a proton barrier. The explanation for the sundry BMC functions must therefore be sought in the characteristics of the pores that traverse their shells.


2011 ◽  
Vol 40 (8) ◽  
pp. 4286 ◽  
Author(s):  
Jonas W. Højfeldt ◽  
Aaron R. Van Dyke ◽  
Anna K. Mapp

2019 ◽  
Vol 11 (19) ◽  
pp. 5541
Author(s):  
Carmelina Bevilacqua ◽  
Ilaria Giada Anversa ◽  
Gianmarco Cantafio ◽  
Pasquale Pizzimenti

The paper aimed at exploring the role of local industrial clusters as a part of an important evidence-based pathway for operationalizing smart specialization policy. Hitherto, the scientific debate has been largely focused on the relationship of clusters with the local business environment to boost competitiveness and has mostly searched for the operationalization of smart specialization policy in economically successful regions. However, the understanding of the role of local clusters (LCs), in terms of cluster industries that serve local businesses and residents, as potential “building-blocks” of Smart Specialization Strategies (S3) still lacks interpretive studies. We proposed a conceptual framework to unveil those factors of LCs that may be enhanced in the S3 policy design, around the concepts of adaptiveness and responsiveness to structural and influencing features of a local economic system. The distinction between Local and Traded clusters, applied in the US context, allows the identification of Local Cluster performance because of the availability of a robust data set. Accordingly, a tool is proposed to investigate those factors that are likely empowering smart specialization strategies: The dynamic SWOT analysis on the case of San Diego provides interesting insights toward building this conceptual framework. The findings may help explain how to relate LCs with smart specialization as building-blocks, based on potential risks and opportunities associated with the local economic system.


2013 ◽  
Vol 10 (80) ◽  
pp. 20120740 ◽  
Author(s):  
Tais A. P. F. Doll ◽  
Senthilkumar Raman ◽  
Raja Dey ◽  
Peter Burkhard

Nanoscale assemblies are a unique class of materials, which can be synthesized from inorganic, polymeric or biological building blocks. The multitude of applications of this class of materials ranges from solar and electrical to uses in food, cosmetics and medicine. In this review, we initially highlight characteristic features of polymeric nanoscale assemblies as well as those built from biological units (lipids, nucleic acids and proteins). We give special consideration to protein nanoassemblies found in nature such as ferritin protein cages, bacterial microcompartments and vaults found in eukaryotic cells and designed protein nanoassemblies, such as peptide nanofibres and peptide nanotubes. Next, we focus on biomedical applications of these nanoscale assemblies, such as cell targeting, drug delivery, bioimaging and vaccine development. In the vaccine development section, we report in more detail the use of virus-like particles and self-assembling polypeptide nanoparticles as new vaccine delivery platforms.


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