Engineering the robustness of industrial microbes through synthetic biology.

Microbial fermentations and bioconversions play a central role in the production of pharmaceuticals, enzymes and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximized carbon flux towards target metabolites regardless of fluctuations in intracellular or extracellular environments. This requires cellular systems that maintain functional stability and dynamic homeostasis in a given physiological state, or manipulate transitions between different physiological states. Stable maintenance or smooth transition can be achieved through engineering of dynamic controllability, modular and hierarchical organization, or functional redundancy, three key features of biological robustness in a cellular system. This review summarizes how synthetic biology can be used to improve the robustness of industrial microbes.

[1]  Shankar Mukherji,et al.  Synthetic biology: understanding biological design from synthetic circuits , 2009, Nature Reviews Genetics.

[2]  Christopher A. Voigt,et al.  Synthetic biology: Engineering Escherichia coli to see light , 2005, Nature.

[3]  Kevin V. Solomon,et al.  Engineering microbes with synthetic biology frameworks. , 2008, Trends in biotechnology.

[4]  Guy Plunkett,et al.  Engineering a reduced Escherichia coli genome. , 2002, Genome research.

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

[6]  W. R. Farmer,et al.  Improving lycopene production in Escherichia coli by engineering metabolic control , 2000, Nature Biotechnology.

[7]  Keith E. J. Tyo,et al.  Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli , 2010, Science.

[8]  L. Serrano,et al.  Engineering Signal Transduction Pathways , 2010, Cell.

[9]  B. Møller Dynamic Metabolons , 2010, Science.

[10]  J. Bähler,et al.  Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation , 2008, Nature Reviews Genetics.

[11]  R Mahadevan,et al.  The degree of redundancy in metabolic genes is linked to mode of metabolism. , 2008, Biophysical journal.

[12]  Jay D. Keasling,et al.  Engineering Static and Dynamic Control of Synthetic Pathways , 2010, Cell.

[13]  R. Moezelaar,et al.  Analysis of acid-stressed Bacillus cereus reveals a major oxidative response and inactivation-associated radical formation. , 2010, Environmental microbiology.

[14]  Víctor de Lorenzo,et al.  Engineering input/output nodes in prokaryotic regulatory circuits. , 2010, FEMS microbiology reviews.

[15]  Jay D. Keasling,et al.  A model for improving microbial biofuel production using a synthetic feedback loop , 2010, Systems and Synthetic Biology.

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

[17]  S. Kanaya,et al.  Enhanced Recombinant Protein Productivity by Genome Reduction in Bacillus subtilis , 2008, DNA research : an international journal for rapid publication of reports on genes and genomes.

[18]  Hiroaki Kitano,et al.  Biological robustness , 2008, Nature Reviews Genetics.

[19]  A. Arkin,et al.  Motifs, modules and games in bacteria. , 2003, Current opinion in microbiology.

[20]  Michelle C. Y. Chang,et al.  Enzyme mechanism as a kinetic control element for designing synthetic biofuel pathways. , 2011, Nature chemical biology.

[21]  A. Regev,et al.  Impulse Control: Temporal Dynamics in Gene Transcription , 2011, Cell.

[22]  Min Lin,et al.  Laboratory-Evolved Mutants of an Exogenous Global Regulator, IrrE from Deinococcus radiodurans, Enhance Stress Tolerances of Escherichia coli , 2011, PloS one.

[23]  Yanping Zhang,et al.  Proteomic Analyses To Reveal the Protective Role of Glutathione in Resistance of Lactococcus lactis to Osmotic Stress , 2010, Applied and Environmental Microbiology.

[24]  G. Church,et al.  Synthetic Gene Networks That Count , 2009, Science.

[25]  Rainer Breitling,et al.  Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms , 2011, Nature Reviews Microbiology.

[26]  H. Kitano Towards a theory of biological robustness , 2007, Molecular systems biology.

[27]  Yin Li,et al.  Engineering the robustness of Clostridium acetobutylicum by introducing glutathione biosynthetic capability. , 2011, Metabolic engineering.

[28]  J. Keasling Manufacturing Molecules Through Metabolic Engineering , 2010, Science.

[29]  L. Looger,et al.  Computational design of receptor and sensor proteins with novel functions , 2003, Nature.

[30]  Pierre Brézellec,et al.  The role of domain redundancy in genetic robustness against null mutations. , 2006, Journal of molecular biology.

[31]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[32]  J. Collins,et al.  Programmable cells: interfacing natural and engineered gene networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. Stephanopoulos,et al.  Engineering for biofuels: exploiting innate microbial capacity or importing biosynthetic potential? , 2009, Nature Reviews Microbiology.

[34]  Fuzhong Zhang,et al.  Biosensors and their applications in microbial metabolic engineering. , 2011, Trends in microbiology.

[35]  Faisal A. Aldaye,et al.  Organization of Intracellular Reactions with Rationally Designed RNA Assemblies , 2011, Science.

[36]  L. Tsimring,et al.  A synchronized quorum of genetic clocks , 2009, Nature.

[37]  J. Collins,et al.  DIVERSITY-BASED, MODEL-GUIDED CONSTRUCTION OF SYNTHETIC GENE NETWORKS WITH PREDICTED FUNCTIONS , 2009, Nature Biotechnology.

[38]  Kevin M. Smith,et al.  Metabolic engineering of Escherichia coli for 1-butanol production. , 2008, Metabolic engineering.

[39]  Christopher A. Voigt,et al.  Programming cells: towards an automated 'Genetic Compiler'. , 2010, Current opinion in biotechnology.

[40]  Jay D. Keasling,et al.  Functional Genomic Study of Exogenous n-Butanol Stress in Escherichia coli , 2010, Applied and Environmental Microbiology.

[41]  J. Stelling,et al.  Robustness of Cellular Functions , 2004, Cell.

[42]  Yan Zhu,et al.  The Importance of Engineering Physiological Functionality into Microbes Opinion , 2022 .

[43]  J. Liao,et al.  Driving Forces Enable High-Titer Anaerobic 1-Butanol Synthesis in Escherichia coli , 2011, Applied and Environmental Microbiology.

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

[45]  Guo-Qiang Chen,et al.  A Microbial Polyhydroxyalkanoates (PHA) Based Bio- and Materials Industry , 2009 .

[46]  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.

[47]  E. Papoutsakis,et al.  A comparative view of metabolite and substrate stress and tolerance in microbial bioprocessing: From biofuels and chemicals, to biocatalysis and bioremediation. , 2010, Metabolic engineering.

[48]  Edward A. Bayer,et al.  Exploration of New Geometries in Cellulosome-Like Chimeras , 2007, Applied and Environmental Microbiology.

[49]  James M Clomburg,et al.  Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals , 2011, Nature.

[50]  Satoshi Omura,et al.  Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism , 2010, Proceedings of the National Academy of Sciences.

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

[52]  F. Blattner,et al.  Emergent Properties of Reduced-Genome Escherichia coli , 2006, Science.

[53]  F. Blattner,et al.  Reduced evolvability of Escherichia coli MDS42, an IS-less cellular chassis for molecular and synthetic biology applications , 2010, Microbial cell factories.

[54]  M. Bennett,et al.  A fast, robust, and tunable synthetic gene oscillator , 2008, Nature.

[55]  Rui-Qiang,et al.  IrrE, a Global Regulator of Extreme Radiation Resistance in Deinococcus radiodurans, Enhances Salt Tolerance in Escherichia coli and Brassica napus , 2009, PloS one.

[56]  M. Win,et al.  Higher-Order Cellular Information Processing with Synthetic RNA Devices , 2008, Science.

[57]  Ahmad S. Khalil,et al.  Synthetic biology: applications come of age , 2010, Nature Reviews Genetics.