Engineering the Bacterial Microcompartment Domain for Molecular Scaffolding Applications

As synthetic biology advances the intricacy of engineered biological systems, the importance of spatial organization within the cellular environment must not be marginalized. Increasingly, biological engineers are investigating means to control spatial organization within the cell, mimicking strategies used by natural pathways to increase flux and reduce cross-talk. A modular platform for constructing a diverse set of defined, programmable architectures would greatly assist in improving yields from introduced metabolic pathways and increasing insulation of other heterologous systems. Here, we review recent research on the shell proteins of bacterial microcompartments and discuss their potential application as “building blocks” for a range of customized intracellular scaffolds. We summarize the state of knowledge on the self-assembly of BMC shell proteins and discuss future avenues of research that will be important to realize the potential of BMC shell proteins as predictively assembling and programmable biological materials for bioengineering.

[1]  T. Pawson,et al.  Signaling through scaffold, anchoring, and adaptor proteins. , 1997, Science.

[2]  Steve Barrett,et al.  Visualization of Bacterial Microcompartment Facet Assembly Using High-Speed Atomic Force Microscopy , 2015, Nano letters.

[3]  Hao Yan,et al.  Challenges and opportunities for structural DNA nanotechnology. , 2011, Nature nanotechnology.

[4]  Seth D. Axen,et al.  A Taxonomy of Bacterial Microcompartment Loci Constructed by a Novel Scoring Method , 2014, PLoS Comput. Biol..

[5]  J. Mccammon,et al.  Channeling by Proximity: The Catalytic Advantages of Active Site Colocalization Using Brownian Dynamics , 2010, The journal of physical chemistry letters.

[6]  H. J. Wagner,et al.  Engineering bacterial microcompartments with heterologous enzyme cargos , 2017, Engineering in life sciences.

[7]  Re-directing bacterial microcompartment systems to enhance recombinant expression of lysis protein E from bacteriophage ϕX174 in Escherichia coli , 2017, Microbial Cell Factories.

[8]  T. Bobik,et al.  Interactions between the termini of lumen enzymes and shell proteins mediate enzyme encapsulation into bacterial microcompartments , 2012, Proceedings of the National Academy of Sciences.

[9]  T. Yeates,et al.  Atomic-Level Models of the Bacterial Carboxysome Shell , 2008, Science.

[10]  C. Kerfeld,et al.  Bacterial microcompartments. , 2010, Annual review of microbiology.

[11]  Daniel P. Mulvihill,et al.  Solution structure of a bacterial microcompartment targeting peptide and its application in the construction of an ethanol bioreactor. , 2014, ACS synthetic biology.

[12]  Martin Phillips,et al.  Protein Structures Forming the Shell of Primitive Bacterial Organelles , 2005, Science.

[13]  Cheryl A Kerfeld,et al.  Bacterial microcompartments and the modular construction of microbial metabolism. , 2015, Trends in microbiology.

[14]  C. Bashor,et al.  Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems. , 2010, Annual review of biophysics.

[15]  Mingzhi Liang,et al.  Synthesis of empty bacterial microcompartments, directed organelle protein incorporation, and evidence of filament-associated organelle movement. , 2010, Molecular cell.

[16]  B. Samborska,et al.  Interactions and structural variability of β-carboxysomal shell protein CcmL , 2014, Photosynthesis Research.

[17]  C. Kerfeld,et al.  Streamlined Construction of the Cyanobacterial CO2-Fixing Organelle via Protein Domain Fusions for Use in Plant Synthetic Biology , 2015, Plant Cell.

[18]  J. Marles-Wright,et al.  Structural Insight into the Clostridium difficile Ethanolamine Utilisation Microcompartment , 2012, PloS one.

[19]  Jason D. Perlmutter,et al.  Many-molecule encapsulation by an icosahedral shell , 2016, eLife.

[20]  P. Silver,et al.  Modularity of a carbon-fixing protein organelle , 2011, Proceedings of the National Academy of Sciences.

[21]  Lu-Ning Liu,et al.  Light Modulates the Biosynthesis and Organization of Cyanobacterial Carbon Fixation Machinery through Photosynthetic Electron Flow1[OPEN] , 2016, Plant Physiology.

[22]  P. J. Andralojc,et al.  β-Carboxysomal proteins assemble into highly organized structures in Nicotiana chloroplasts. , 2014, The Plant journal : for cell and molecular biology.

[23]  Ned S Wingreen,et al.  Enzyme clustering accelerates processing of intermediates through metabolic channeling , 2014, Nature Biotechnology.

[24]  Structure of a novel 13 nm dodecahedral nanocage assembled from a redesigned bacterial microcompartment shell protein. , 2016, Chemical communications.

[25]  Cameron Myhrvold,et al.  Using synthetic RNAs as scaffolds and regulators , 2015, Nature Structural &Molecular Biology.

[26]  Jeffrey D Varner,et al.  Engineering the spatial organization of metabolic enzymes: mimicking nature's synergy. , 2008, Current opinion in biotechnology.

[27]  Todd O Yeates,et al.  Bacterial microcompartment organelles: protein shell structure and evolution. , 2010, Annual review of biophysics.

[28]  C. Kerfeld,et al.  Purification and Characterization of Protein Nanotubes Assembled from a Single Bacterial Microcompartment Shell Subunit , 2016 .

[29]  Hao Yan,et al.  Interenzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures. , 2012, Journal of the American Chemical Society.

[30]  Pamela A Silver,et al.  Natural strategies for the spatial optimization of metabolism in synthetic biology. , 2012, Nature chemical biology.

[31]  Gabriel C. Wu,et al.  Synthetic protein scaffolds provide modular control over metabolic flux , 2009, Nature Biotechnology.

[32]  Cheryl A Kerfeld,et al.  The Structure of CcmP, a Tandem Bacterial Microcompartment Domain Protein from the β-Carboxysome, Forms a Subcompartment Within a Microcompartment , 2013, The Journal of Biological Chemistry.

[33]  Andrew Bleloch,et al.  Biochemical and Structural Insights into Bacterial Organelle Form and Biogenesis* , 2008, Journal of Biological Chemistry.

[34]  Peng Yin,et al.  Genetic encoding of DNA nanostructures and their self-assembly in living bacteria , 2016, Nature Communications.

[35]  Claudia Schmidt-Dannert,et al.  Engineered Protein Nano-Compartments for Targeted Enzyme Localization , 2012, PloS one.

[36]  Ka-Hei Siu,et al.  Synthetic scaffolds for pathway enhancement. , 2015, Current opinion in biotechnology.

[37]  K. Dill,et al.  An iterative method for extracting energy-like quantities from protein structures. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Itamar Willner,et al.  Enzyme cascades activated on topologically programmed DNA scaffolds. , 2009, Nature nanotechnology.

[39]  D. Clark,et al.  Protein Calligraphy: A New Concept Begins To Take Shape , 2016, ACS central science.

[40]  Q. Luo,et al.  Protein Assembly: Versatile Approaches to Construct Highly Ordered Nanostructures. , 2016, Chemical reviews.

[41]  Crystallographic Insights into the Pore Structures and Mechanisms of the EutL and EutM Shell Proteins of the Ethanolamine-Utilizing Microcompartment of Escherichia coli , 2010, Journal of bacteriology.

[42]  Scott Calabrese Barton,et al.  Substrate channelling as an approach to cascade reactions. , 2016, Nature chemistry.

[43]  Henry Hess,et al.  Engineering enzymatic cascades on nanoscale scaffolds. , 2013, Current opinion in biotechnology.

[44]  T. Yeates,et al.  Two‐dimensional crystals of carboxysome shell proteins recapitulate the hexagonal packing of three‐dimensional crystals , 2009, Protein science : a publication of the Protein Society.

[45]  Mojca Benčina,et al.  DNA-guided assembly of biosynthetic pathways promotes improved catalytic efficiency , 2011, Nucleic acids research.

[46]  C. Schmidt-Dannert,et al.  Engineering formation of multiple recombinant Eut protein nanocompartments in E. coli , 2016, Scientific Reports.

[47]  J. Séquaris,et al.  Principles of Protein , 1980 .

[48]  Christopher M. Jakobson,et al.  Localization of Proteins to the 1,2-Propanediol Utilization Microcompartment by Non-native Signal Sequences Is Mediated by a Common Hydrophobic Motif* , 2015, The Journal of Biological Chemistry.

[49]  R. Pickersgill,et al.  Structural Insights into Higher Order Assembly and Function of the Bacterial Microcompartment Protein PduA* , 2014, The Journal of Biological Chemistry.

[50]  T. Yeates,et al.  The function of the PduJ microcompartment shell protein is determined by the genomic position of its encoding gene , 2016, Molecular microbiology.

[51]  P. Silver,et al.  Spatially Ordered Dynamics of the Bacterial Carbon Fixation Machinery , 2010, Science.

[52]  Martin J. Warren,et al.  Employing bacterial microcompartment technology to engineer a shell-free enzyme-aggregate for enhanced 1,2-propanediol production in Escherichia coli , 2016, Metabolic engineering.

[53]  M. Prentice,et al.  Bacterial microcompartment-directed polyphosphate kinase promotes stable polyphosphate accumulation in E. coli. , 2017, Biotechnology journal.

[54]  Arvind Murugan,et al.  Undesired usage and the robust self-assembly of heterogeneous structures , 2015, Nature Communications.

[55]  T. Yeates,et al.  Structural Insight into the Mechanisms of Transport across the Salmonella enterica Pdu Microcompartment Shell* , 2010, The Journal of Biological Chemistry.

[56]  Xiaolin Cheng,et al.  Theoretical Study of the Initial Stages of Self-Assembly of a Carboxysome's Facet. , 2016, ACS nano.

[57]  C. Kerfeld,et al.  Assembly principles and structure of a 6.5-MDa bacterial microcompartment shell , 2017, Science.

[58]  S. Howorka.  Rationally engineering natural protein assemblies in nanobiotechnology. , 2011, Current opinion in biotechnology.

[59]  C. Kerfeld,et al.  Engineering bacterial microcompartment shells: chimeric shell proteins and chimeric carboxysome shells. , 2015, ACS synthetic biology.

[60]  Edward Y. Kim,et al.  A rapid flow cytometry assay for the relative quantification of protein encapsulation into bacterial microcompartments. , 2014, Biotechnology journal.

[61]  Wendell A. Lim,et al.  Scaffold Proteins: Hubs for Controlling the Flow of Cellular Information , 2011, Science.

[62]  T. Yeates,et al.  Insights from multiple structures of the shell proteins from the β‐carboxysome , 2008, Protein science : a publication of the Protein Society.

[63]  Christopher M. Jakobson,et al.  Evidence for Improved Encapsulated Pathway Behavior in a Bacterial Microcompartment through Shell Protein Engineering. , 2017, ACS synthetic biology.

[64]  C. Kerfeld,et al.  Production and Characterization of Synthetic Carboxysome Shells with Incorporated Luminal Proteins1[OPEN] , 2016, Plant Physiology.

[65]  Julia Frunzke,et al.  Heterologous expression of the Halothiobacillus neapolitanus carboxysomal gene cluster in Corynebacterium glutamicum. , 2017, Journal of biotechnology.

[66]  Heinrich Sticht,et al.  Synthetic Protein Scaffolds Based on Peptide Motifs and Cognate Adaptor Domains for Improving Metabolic Productivity , 2015, Front. Bioeng. Biotechnol..

[67]  William C. Deloache,et al.  Spatial organization of enzymes for metabolic engineering. , 2012, Metabolic engineering.

[68]  C. Kerfeld,et al.  Elucidating Essential Role of Conserved Carboxysomal Protein CcmN Reveals Common Feature of Bacterial Microcompartment Assembly* , 2012, The Journal of Biological Chemistry.

[69]  C. Schmidt-Dannert,et al.  Encapsulation of multiple cargo proteins within recombinant Eut nanocompartments , 2016, Applied Microbiology and Biotechnology.

[70]  S. Teichmann,et al.  Principles of assembly reveal a periodic table of protein complexes , 2015, Science.

[71]  Todd O Yeates,et al.  Alanine scanning mutagenesis identifies an asparagine-arginine-lysine triad essential to assembly of the shell of the Pdu microcompartment. , 2014, Journal of molecular biology.

[72]  Cheryl A Kerfeld,et al.  Assembly of robust bacterial microcompartment shells using building blocks from an organelle of unknown function. , 2014, Journal of molecular biology.

[73]  Cheryl A Kerfeld,et al.  Identification and structural analysis of a novel carboxysome shell protein with implications for metabolite transport. , 2009, Journal of molecular biology.

[74]  Pamela A Silver,et al.  Encapsulation as a Strategy for the Design of Biological Compartmentalization. , 2016, Journal of molecular biology.

[75]  Thomas A. Bobik,et al.  PduA Is a Shell Protein of Polyhedral Organelles Involved in Coenzyme B12-Dependent Degradation of 1,2-Propanediol in Salmonella enterica Serovar Typhimurium LT2 , 2002, Journal of bacteriology.

[76]  Jeffrey C. Cameron,et al.  Biogenesis of a Bacterial Organelle: The Carboxysome Assembly Pathway , 2013, Cell.

[77]  C. Kerfeld,et al.  Bacterial microcompartment assembly: The key role of encapsulation peptides , 2015, Communicative & integrative biology.

[78]  R. Nussinov,et al.  Principles of protein-protein interactions: what are the preferred ways for proteins to interact? , 2008, Chemical reviews.

[79]  B. Samborska,et al.  A dodecameric CcmK2 structure suggests β-carboxysomal shell facets have a double-layered organization. , 2012, Structure.

[80]  R. Pickersgill,et al.  Structure of a trimeric bacterial microcompartment shell protein, EtuB, associated with ethanol utilization in Clostridium kluyveri. , 2009, The Biochemical journal.

[81]  H. Dietz,et al.  Placing molecules with Bohr radius resolution using DNA origami. , 2016, Nature nanotechnology.

[82]  C. Kerfeld,et al.  Comparative analysis of carboxysome shell proteins , 2011, Photosynthesis Research.