Resource Reallocation in Bacteria by Reengineering the Gene Expression Machinery.

Bacteria have evolved complex regulatory networks to control the activity of transcription and translation, and thus the growth rate, over a range of environmental conditions. Reengineering RNA polymerase and ribosomes allows modifying naturally evolved regulatory networks and thereby profoundly reorganizing the manner in which bacteria allocate resources to different cellular functions. This opens new opportunities for our fundamental understanding of microbial physiology and for a variety of applications. Recent breakthroughs in genome engineering and the miniaturization and automation of culturing methods have offered new perspectives for the reengineering of the transcription and translation machinery in bacteria as well as the development of novel in vitro and in vivo gene expression systems. We review different examples from the unifying perspective of resource reallocation, and discuss the impact of these approaches for microbial systems biology and biotechnological applications.

[1]  P. Holliger,et al.  Polymerase engineering: towards the encoded synthesis of unnatural biopolymers. , 2009, Chemical communications.

[2]  K. Ochi,et al.  Activation of Antibiotic Biosynthesis by Specified Mutations in the rpoB Gene (Encoding the RNA Polymerase β Subunit) of Streptomyces lividans , 2002, Journal of bacteriology.

[3]  Christopher A. Voigt,et al.  Design of orthogonal genetic switches based on a crosstalk map of σs, anti-σs, and promoters , 2013, Molecular Systems Biology.

[4]  James Chappell,et al.  Creating small transcription activating RNAs. , 2015, Nature chemical biology.

[5]  Antoine Danchin,et al.  Scaling up synthetic biology: Do not forget the chassis , 2012, FEBS letters.

[6]  B. Teusink,et al.  Shifts in growth strategies reflect tradeoffs in cellular economics , 2009, Molecular systems biology.

[7]  Jim Swartz,et al.  Developing cell-free biology for industrial applications , 2006, Journal of Industrial Microbiology and Biotechnology.

[8]  Zhanglin Lin,et al.  Bacterial Sigma Factors as Targets for Engineered or Synthetic Transcriptional Control , 2014, Front. Bioeng. Biotechnol..

[9]  Henrike Niederholtmeyer,et al.  Rapid cell-free forward engineering of novel genetic ring oscillators , 2015, eLife.

[10]  Thomas H. Segall-Shapiro,et al.  Modular control of multiple pathways using engineered orthogonal T7 polymerases , 2012, Nucleic acids research.

[11]  Piotr Garstecki,et al.  Droplet microfluidics for microbiology: techniques, applications and challenges. , 2016, Lab on a chip.

[12]  C. Kurland,et al.  Translational accuracy and the fitness of bacteria. , 1992, Annual review of genetics.

[13]  T. Nyström,et al.  Increased RNA polymerase availability directs resources towards growth at the expense of maintenance , 2009, The EMBO journal.

[14]  C. Kurland,et al.  Bacterial growth inhibition by overproduction of protein , 1996, Molecular microbiology.

[15]  K. Ochi,et al.  From Microbial Differentiation to Ribosome Engineering , 2007, Bioscience, biotechnology, and biochemistry.

[16]  Edward J. O'Brien,et al.  Use of Adaptive Laboratory Evolution To Discover Key Mutations Enabling Rapid Growth of Escherichia coli K-12 MG1655 on Glucose Minimal Medium , 2014, Applied and Environmental Microbiology.

[17]  T. Hwa,et al.  Interdependence of Cell Growth and Gene Expression: Origins and Consequences , 2010, Science.

[18]  Robert W. Bradley,et al.  Designer cell signal processing circuits for biotechnology , 2015, New biotechnology.

[19]  Fabio Rinaldi,et al.  RegulonDB version 9.0: high-level integration of gene regulation, coexpression, motif clustering and beyond , 2015, Nucleic Acids Res..

[20]  Marshall W. Nirenberg,et al.  The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides , 1961, Proceedings of the National Academy of Sciences.

[21]  Ron Weiss,et al.  Isocost Lines Describe the Cellular Economy of Genetic Circuits , 2015, Biophysical journal.

[22]  Dong-Myung Kim,et al.  Implementing bacterial acid resistance into cell-free protein synthesis for buffer-free expression and screening of enzymes. , 2015, Biotechnology and bioengineering.

[23]  T. Ueda,et al.  Purified cell-free systems as standard parts for synthetic biology. , 2014, Current opinion in chemical biology.

[24]  David R. Liu,et al.  Negative selection and stringency modulation in phage-assisted constinuous evolution , 2014, Nature chemical biology.

[25]  Víctor de Lorenzo,et al.  Synthetic bugs on the loose: containment options for deeply engineered (micro)organisms. , 2016, Current opinion in biotechnology.

[26]  Byung-Kwan Cho,et al.  RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media , 2010, Proceedings of the National Academy of Sciences.

[27]  J. Micklefield,et al.  Dual transcriptional-translational cascade permits cellular level tuneable expression control , 2015, Nucleic acids research.

[28]  Andrew D. Ellington,et al.  Directed evolution of genetic parts and circuits by compartmentalized partnered replication , 2013, Nature Biotechnology.

[29]  V. Noireaux,et al.  Genetically expanded cell‐free protein synthesis using endogenous pyrrolysyl orthogonal translation system , 2015, Biotechnology and bioengineering.

[30]  O. Maaløe,et al.  Dependency on medium and temperature of cell size and chemical composition during balanced grown of Salmonella typhimurium. , 1958, Journal of general microbiology.

[31]  G. Stephanopoulos,et al.  Engineering Yeast Transcription Machinery for Improved Ethanol Tolerance and Production , 2006, Science.

[32]  G. Stan,et al.  Quantifying cellular capacity identifies gene expression designs with reduced burden , 2015, Nature Methods.

[33]  J. Keasling,et al.  Engineering dynamic pathway regulation using stress-response promoters , 2013, Nature Biotechnology.

[34]  Christian Hoffmeister,et al.  Cotranslational incorporation of non‐standard amino acids using cell‐free protein synthesis , 2015, FEBS letters.

[35]  V. Noireaux,et al.  An E. coli cell-free expression toolbox: application to synthetic gene circuits and artificial cells. , 2012, ACS synthetic biology.

[36]  C. J. Murray,et al.  Microscale to Manufacturing Scale-up of Cell-Free Cytokine Production—A New Approach for Shortening Protein Production Development Timelines , 2011, Biotechnology and bioengineering.

[37]  Julius B Lucks,et al.  Engineered Protein Machines: Emergent Tools for Synthetic Biology. , 2016, Cell chemical biology.

[38]  A. Spirin High-throughput cell-free systems for synthesis of functionally active proteins. , 2004, Trends in biotechnology.

[39]  G. Church,et al.  Overcoming Challenges in Engineering the Genetic Code. , 2016, Journal of molecular biology.

[40]  C. J. Murray,et al.  Production of site-specific antibody-drug conjugates using optimized non-natural amino acids in a cell-free expression system. , 2014, Bioconjugate chemistry.

[41]  Michael C. Jewett,et al.  Protein synthesis by ribosomes with tethered subunits , 2015, Nature.

[42]  J. Keasling,et al.  Engineering Cellular Metabolism , 2016, Cell.

[43]  Rui Gan,et al.  Cell-free protein synthesis: applications come of age. , 2012, Biotechnology advances.

[44]  V. Fromion,et al.  Translation elicits a growth rate‐dependent, genome‐wide, differential protein production in Bacillus subtilis , 2016, Molecular systems biology.

[45]  Qi-li Zhu,et al.  Using global transcription machinery engineering (gTME) to improve ethanol tolerance of Zymomonas mobilis , 2016, Microbial Cell Factories.

[46]  Manuel A. S. Santos,et al.  Non-Standard Genetic Codes Define New Concepts for Protein Engineering , 2015, Life.

[47]  Jean-Luc Gouzé,et al.  Dynamical Allocation of Cellular Resources as an Optimal Control Problem: Novel Insights into Microbial Growth Strategies , 2016, PLoS Comput. Biol..

[48]  Tamás Fehér,et al.  System-level genome editing in microbes. , 2016, Current opinion in microbiology.

[49]  F. Studier,et al.  Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. , 1986, Journal of molecular biology.

[50]  David R. Liu,et al.  A System for the Continuous Directed Evolution of Biomolecules , 2011, Nature.

[51]  J. Collado-Vides,et al.  The EcoCyc Database. , 2018, EcoSal Plus.

[52]  V. Sperandio,et al.  Cell-to-Cell Signaling in Escherichia coli and Salmonella , 2013, EcoSal Plus.

[53]  P. Alifano,et al.  Rifampicin-resistance, rpoB polymorphism and RNA polymerase genetic engineering. , 2015, Journal of biotechnology.

[54]  U. Sauer,et al.  Coordination of microbial metabolism , 2014, Nature Reviews Microbiology.

[55]  Judy Qiu,et al.  Total Synthesis of a Functional Designer Eukaryotic Chromosome , 2014, Science.

[56]  Víctor de Lorenzo Beware of metaphors: chasses and orthogonality in synthetic biology. , 2011 .

[57]  J. Chin,et al.  Synthesis of orthogonal transcription-translation networks , 2009, Proceedings of the National Academy of Sciences.

[58]  Manish Kushwaha,et al.  A portable expression resource for engineering cross-species genetic circuits and pathways , 2015, Nature Communications.

[59]  G. Stephanopoulos,et al.  Improving fatty acids production by engineering dynamic pathway regulation and metabolic control , 2014, Proceedings of the National Academy of Sciences.

[60]  A. Ellington,et al.  Directed Evolution of a Panel of Orthogonal T7 RNA Polymerase Variants for in Vivo or in Vitro Synthetic Circuitry. , 2015, ACS synthetic biology.

[61]  Irene M Ong,et al.  Correcting direct effects of ethanol on translation and transcription machinery confers ethanol tolerance in bacteria , 2014, Proceedings of the National Academy of Sciences.

[62]  Arne G. Schmeisky,et al.  Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium , 2015, Molecular systems biology.

[63]  M L Shuler,et al.  Considerations for the design and construction of a synthetic platform cell for biotechnological applications. , 2010, Biotechnology and bioengineering.

[64]  Henrike Niederholtmeyer,et al.  Implementation of cell-free biological networks at steady state , 2013, Proceedings of the National Academy of Sciences.

[65]  H. Alper,et al.  Using transcription machinery engineering to elicit complex cellular phenotypes. , 2012, Methods in molecular biology.

[66]  Tetsuya Yomo,et al.  In vitro membrane protein synthesis inside cell-sized vesicles reveals the dependence of membrane protein integration on vesicle volume. , 2014, ACS synthetic biology.

[67]  S. L. Mayo,et al.  Cell‐free protein synthesis enables high yielding synthesis of an active multicopper oxidase , 2016, Biotechnology journal.

[68]  Quanfeng Liang,et al.  Construction of stress-induced metabolic pathway from glucose to 1,3-propanediol in Escherichia coli , 2010, Applied Microbiology and Biotechnology.

[69]  Vincent Noireaux,et al.  A cost-effective polyphosphate-based metabolism fuels an all E. coli cell-free expression system. , 2015, Metabolic engineering.

[70]  Ronald Levy,et al.  A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity , 2012, Proceedings of the National Academy of Sciences.

[71]  Peter G. Schultz,et al.  Genomically Recoded Organisms Expand Biological Functions , 2013, Science.

[72]  Johannes Geiselmann,et al.  A synthetic growth switch based on controlled expression of RNA polymerase , 2015, Molecular systems biology.

[73]  Adam J. Meyer,et al.  A ‘resource allocator’ for transcription based on a highly fragmented T7 RNA polymerase , 2014, Molecular systems biology.

[74]  Michael C Jewett,et al.  An integrated cell-free metabolic platform for protein production and synthetic biology , 2008, Molecular systems biology.

[75]  Zachary Z. Sun,et al.  Characterizing and prototyping genetic networks with cell-free transcription-translation reactions. , 2015, Methods.

[76]  Bradley C. Bundy,et al.  The emerging age of cell‐free synthetic biology , 2014, FEBS letters.

[77]  Isabel Rocha,et al.  Systems Biology Perspectives on Minimal and Simpler Cells , 2014, Microbiology and Molecular Reviews.

[78]  P. Swain,et al.  Mechanistic links between cellular trade-offs, gene expression, and growth , 2015, Proceedings of the National Academy of Sciences.

[79]  M. Khammash,et al.  Automated optogenetic feedback control for precise and robust regulation of gene expression and cell growth , 2016, Nature Communications.

[80]  Takuya Ueda,et al.  Cell-free translation reconstituted with purified components , 2001, Nature Biotechnology.

[81]  B. E. Kimmel,et al.  Optimized clinical performance of growth hormone with an expanded genetic code , 2011, Proceedings of the National Academy of Sciences.

[82]  A. Hatch,et al.  A general strategy for expanding polymerase function by droplet microfluidics , 2016, Nature Communications.

[83]  G. Stephanopoulos,et al.  Assessing the potential of mutational strategies to elicit new phenotypes in industrial strains , 2008, Proceedings of the National Academy of Sciences.

[84]  G. Stephanopoulos,et al.  Global transcription machinery engineering: a new approach for improving cellular phenotype. , 2007, Metabolic engineering.

[85]  Gerald Striedner,et al.  Preventing T7 RNA polymerase read-through transcription-A synthetic termination signal capable of improving bioprocess stability. , 2015, ACS synthetic biology.

[86]  M. Jewett,et al.  Mimicking the Escherichia coli cytoplasmic environment activates long‐lived and efficient cell‐free protein synthesis , 2004, Biotechnology and bioengineering.

[87]  Vincent Noireaux,et al.  Development of an artificial cell, from self-organization to computation and self-reproduction , 2011 .

[88]  B. Cooperman,et al.  Engine out of the chassis: Cell‐free protein synthesis and its uses , 2014, FEBS letters.

[89]  George M Church,et al.  Towards synthesis of a minimal cell , 2006, Molecular systems biology.

[90]  Farren J. Isaacs,et al.  Recoded organisms engineered to depend on synthetic amino acids , 2015, Nature.

[91]  Ke Chen,et al.  Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution. , 2016, Cell systems.

[92]  C. Gross,et al.  Multiple sigma subunits and the partitioning of bacterial transcription space. , 2003, Annual review of microbiology.

[93]  J. Chin,et al.  A network of orthogonal ribosome·mRNA pairs , 2005, Nature chemical biology.

[94]  T. Hwa,et al.  Emergence of robust growth laws from optimal regulation of ribosome synthesis , 2014, Molecular systems biology.

[95]  Masaru Tomita,et al.  Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol , 2014, Nature Communications.

[96]  G. Church,et al.  Large-scale de novo DNA synthesis: technologies and applications , 2014, Nature Methods.

[97]  Andrew D Ellington,et al.  Addicting diverse bacteria to a noncanonical amino acid. , 2016, Nature chemical biology.

[98]  Lars M Blank,et al.  Grand challenge commentary: Chassis cells for industrial biochemical production. , 2010, Nature chemical biology.

[99]  Wei Suong Teo,et al.  A Two-Layer Gene Circuit for Decoupling Cell Growth from Metabolite Production. , 2016, Cell systems.

[100]  A. Matin,et al.  Use of starvation promoters to limit growth and selectively enrich expression of trichloroethylene- and phenol-transforming activity in recombinant Escherichia coli [corrected] , 1995, Applied and environmental microbiology.