Review Article | Published:

Synthetic biology: applications come of age

Nature Reviews Genetics 11, 367–379 (2010) | Download Citation

Subjects

Abstract

Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.

Key points

  • Early synthetic biology designs, namely the genetic toggle switch and repressilator, showed that regulatory components can be characterized and assembled to bring about complex, electronics-inspired behaviours in living systems (for example, memory storage and timekeeping).

  • Through the characterization and assembly of genetic parts and biological building blocks, many more devices have been constructed, including switches, memory elements, oscillators, pulse generators, digital logic gates, filters and communication modules.

  • Advances in the field are now allowing expansion beyond small gene networks to the realm of larger biological programs, which hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials.

  • Synthetic biosensing circuits consist of sensitive elements that bind analytes and transducer modules that mobilize cellular responses. Balancing these two modules involves engineering modularity and specificity into the various circuits.

  • Biosensor sensitive elements include environment-responsive promoters (transcriptional), RNA aptamers (translational) and protein receptors (post-translational).

  • Biosensor transducer modules include engineered gene networks (transcriptional), non-coding regulatory RNAs (translational) and protein signal-transduction circuits (post-translational).

  • The contributions of synthetic biology to therapeutics include: engineered networks and organisms for disease-mechanism elucidation, drug-target identification, drug-discovery platforms, therapeutic treatment, therapeutic delivery, and drug production and access.

  • In the microbial production of biofuels and pharmaceuticals, synthetic biology has supplemented traditional genetic and metabolic engineering efforts by aiding the construction of optimized biosynthetic pathways.

  • Optimizing metabolic flux through biosynthetic pathways is traditionally accomplished by driving the expression of pathway enzymes with strong, inducible promoters. New synthetic approaches include the rapid diversification of various pathway components, the rational and model-guided assembly of pathway components, and hybrid solutions.

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References

  1. 1.

    & General conclusions: telenomic mechanisms in cellular metabolism, growth, and differentiation. Cold Spring Harb. Symp. Quant. Biol. 26, 389–401 (1961).

  2. 2.

    & The logical analysis of continuous, non-linear biochemical control networks. J. Theor. Biol. 39, 103–129 (1973).

  3. 3.

    Comparison of classical and autogenous systems of regulation in inducible operons. Nature 252, 546–549 (1974).

  4. 4.

    The large scale structure and dynamics of gene control circuits: an ensemble approach. J. Theor. Biol. 44, 167–190 (1974).

  5. 5.

    Classification of biological networks by their qualitative dynamics. J. Theor. Biol. 54, 85–107 (1975).

  6. 6.

    & Towards a circuit engineering discipline. Curr. Biol. 10, R318–R320 (2000).

  7. 7.

    & Circuit simulation of genetic networks. Science 269, 650–656 (1995).

  8. 8.

    , & Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).

  9. 9.

    & A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000). References 8 and 9 describe synthetic biology's first devices — the genetic toggle switch and the repressilator — and establish the engineering-based methodology for constructing sophisticated, dynamic behaviours in biological systems from simple regulatory elements.

  10. 10.

    , , & Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli. Cell 113, 597–607 (2003).

  11. 11.

    & Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nature Biotech. 23, 337–343 (2005). This paper establishes an RNA scaffold for the ligand-dependent ON–OFF switching of gene expression.

  12. 12.

    , & A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells. Cell 130, 363–372 (2007).

  13. 13.

    , , & Reprogramming control of an allosteric signaling switch through modular recombination. Science 301, 1904–1908 (2003). The authors provide a modular framework for programming the input–output behaviour of eukaryotic signalling-protein circuits, and construct synthetic switch proteins with a rich set of gating behaviours.

  14. 14.

    et al. Synthetic gene networks that count. Science 324, 1199–1202 (2009).

  15. 15.

    , , & A tightly regulated inducible expression system utilizing the fim inversion recombination switch. Biotechnol. Bioeng. 94, 1–4 (2006).

  16. 16.

    , , & Design and construction of a double inversion recombination switch for heritable sequential genetic memory. PLoS ONE 3, e2815 (2008).

  17. 17.

    & Hysteresis in a synthetic mammalian gene network. Proc. Natl Acad. Sci. USA 102, 9517–9522 (2005).

  18. 18.

    et al. An engineered epigenetic transgene switch in mammalian cells. Nature Biotech. 22, 867–870 (2004).

  19. 19.

    et al. Rational design of memory in eukaryotic cells. Genes Dev. 21, 2271–2276 (2007).

  20. 20.

    et al. A synthetic gene-metabolic oscillator. Nature 435, 118–122 (2005).

  21. 21.

    et al. A fast, robust and tunable synthetic gene oscillator. Nature 456, 516–519 (2008).

  22. 22.

    , , & A tunable synthetic mammalian oscillator. Nature 457, 309–312 (2009).

  23. 23.

    , , & A synchronized quorum of genetic clocks. Nature 463, 326–330 (2010).

  24. 24.

    , , , & Spatiotemporal control of gene expression with pulse-generating networks. Proc. Natl Acad. Sci. USA 101, 6355–6360 (2004).

  25. 25.

    , & Environmental signal integration by a modular AND gate. Mol. Syst. Biol. 3, 133 (2007).

  26. 26.

    , , & Combinatorial synthesis of genetic networks. Science 296, 1466–1470 (2002).

  27. 27.

    & Cellular logic with orthogonal ribosomes. J. Am. Chem. Soc. 127, 17584–17585 (2005).

  28. 28.

    et al. A universal RNAi-based logic evaluator that operates in mammalian cells. Nature Biotech. 25, 795–801 (2007).

  29. 29.

    & A deoxyribozyme-based molecular automaton. Nature Biotech. 21, 1069–1074 (2003).

  30. 30.

    & Higher-order cellular information processing with synthetic RNA devices. Science 322, 456–460 (2008).

  31. 31.

    , , , & A synthetic multicellular system for programmed pattern formation. Nature 434, 1130–1134 (2005). An excellent demonstration of synthetic control over a population of cells. By splitting the V. fischeri quorum-sensing circuit between 'sender' and 'receiver' cells, bacteria were programmed to communicate to generate intricate two-dimensional patterns.

  32. 32.

    , & Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc. Natl Acad. Sci. USA 102, 3581–3586 (2005).

  33. 33.

    et al. An externally tunable bacterial band-pass filter. Proc. Natl Acad. Sci. USA 106, 10135–10140 (2009).

  34. 34.

    et al. Programmable cells: interfacing natural and engineered gene networks. Proc. Natl Acad. Sci. USA 101, 8414–8419 (2004).

  35. 35.

    , , & Programmed population control by cell–cell communication and regulated killing. Nature 428, 868–871 (2004).

  36. 36.

    & Synthetic biology: understanding biological design from synthetic circuits. Nature Rev. Genet. 10, 859–871 (2009).

  37. 37.

    et al. Lac repressor can regulate expression from a hybrid SV40 early promoter containing a lac operator in animal cells. Cell 49, 603–612 (1987).

  38. 38.

    et al. Regulated expression of foreign genes in mammalian cells under the control of coliphage T3 RNA polymerase and lac repressor. Proc. Natl Acad. Sci. USA 86, 5400–5404 (1989).

  39. 39.

    & The inducible lac operator–repressor system is functional in mammalian cells. Cell 48, 555–566 (1987).

  40. 40.

    & Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1–I2 regulatory elements. Nucleic Acids Res. 25, 1203–1210 (1997).

  41. 41.

    et al. Streptogramin-based gene regulation systems for mammalian cells. Nature Biotech. 18, 1203–1208 (2000).

  42. 42.

    & Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl Acad. Sci. USA 89, 5547–5551 (1992).

  43. 43.

    et al. Macrolide-based transgene control in mammalian cells and mice. Nature Biotech. 20, 901–907 (2002).

  44. 44.

    et al. A novel, inducible, eukaryotic gene expression system based on the quorum-sensing transcription factor TraR. EMBO Rep. 4, 159–165 (2003).

  45. 45.

    et al. Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice. Nucleic Acids Res. 31, e71 (2003).

  46. 46.

    et al. A novel mammalian expression system derived from components coordinating nicotine degradation in arthrobacter nicotinovorans pAO1. Nucleic Acids Res. 33, e107 (2005).

  47. 47.

    et al. The cumate gene-switch: a system for regulated expression in mammalian cells. BMC Biotechnol. 6, 43 (2006).

  48. 48.

    , & A genetic redox sensor for mammalian cells. Metab. Eng. 8, 273–280 (2006).

  49. 49.

    et al. Gas-inducible transgene expression in mammalian cells and mice. Nature Biotech. 22, 1440–1444 (2004).

  50. 50.

    et al. A temperature-regulated replicon-based DNA expression system. Nature Biotech. 18, 429–432 (2000).

  51. 51.

    et al. Conditional human VEGF-mediated vascularization in chicken embryos using a novel temperature-inducible gene regulation (TIGR) system. Nucleic Acids Res. 31, e69 (2003).

  52. 52.

    et al. A synthetic mammalian electro-genetic transcription circuit. Nucleic Acids Res. 37, e33 (2009).

  53. 53.

    Non-coding RNA genes and the modern RNA world. Nature Rev. Genet. 2, 919–929 (2001).

  54. 54.

    & The chemical repertoire of natural ribozymes. Nature 418, 222–228 (2002).

  55. 55.

    , , , & The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857 (1983).

  56. 56.

    et al. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31, 147–157 (1982).

  57. 57.

    , & The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993).

  58. 58.

    , & RNAs involved in copy-number control and incompatibility of plasmid R1. Proc. Natl Acad. Sci. USA 78, 6008–6012 (1981).

  59. 59.

    & Antisense RNA control in bacteria, phages, and plasmids. Annu. Rev. Microbiol. 48, 713–742 (1994).

  60. 60.

    , & RNA synthetic biology. Nature Biotech. 24, 545–554 (2006).

  61. 61.

    , , , & A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes. Trends Genet. 15, 439–442 (1999).

  62. 62.

    et al. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551–561 (2002).

  63. 63.

    & A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates function by forming alternative structures. Proc. Natl Acad. Sci. USA 97, 9919–9924 (2000).

  64. 64.

    , & Regulation and mode of action of the second small RNA activator of RpoS translation, RprA. Mol. Microbiol. 46, 813–826 (2002).

  65. 65.

    , , , & Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 113, 577–586 (2003).

  66. 66.

    et al. Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell 111, 747–756 (2002).

  67. 67.

    et al. Translational induction of heat shock transcription factor σ32: evidence for a built-in RNA thermosensor. Genes Dev. 13, 655–665 (1999).

  68. 68.

    , & Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419, 952–956 (2002).

  69. 69.

    , , , & Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428, 281–286 (2004).

  70. 70.

    & Regulation of bacterial gene expression by riboswitches. Annu. Rev. Microbiol. 59, 487–517 (2005).

  71. 71.

    Translation repression by antisense sequences. Cell. Mol. Life Sci. 60, 854–861 (2003).

  72. 72.

    et al. Automated selection of aptamers against protein targets translated in vitro: from gene to aptamer. Nucleic Acids Res. 30, e108 (2002).

  73. 73.

    & In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990).

  74. 74.

    & Adaptive recognition by nucleic acid aptamers. Science 287, 820–825 (2000).

  75. 75.

    & Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505–510 (1990).

  76. 76.

    et al. Exogenous control of mammalian gene expression through modulation of RNA self-cleavage. Nature 431, 471–476 (2004).

  77. 77.

    , , & Computational design of receptor and sensor proteins with novel functions. Nature 423, 185–190 (2003).

  78. 78.

    et al. Rewiring the specificity of two-component signal transduction systems. Cell 133, 1043–1054 (2008).

  79. 79.

    , , & Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Science 319, 1539–1543 (2008).

  80. 80.

    et al. Synthetic biology: engineering Escherichia coli to see light. Nature 438, 441–442 (2005).

  81. 81.

    , , & Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461, 997–1001 (2009).

  82. 82.

    et al. A synthetic genetic edge detection program. Cell 137, 1272–1281 (2009). An outstanding example of how smaller circuits can be combined to realize larger genetic programs with sophisticated and predictable behaviour. Here, logic gates and cell–cell communication modules were coupled to program a population of bacteria to sense and trace the edges of a projected image.

  83. 83.

    et al. Mutations of the Igβ gene cause agammaglobulinemia in man. J. Exp. Med. 204, 2047–2051 (2007).

  84. 84.

    et al. Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. Proc. Natl Acad. Sci. USA 105, 19944–19949 (2008).

  85. 85.

    et al. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310, 77–80 (2005).

  86. 86.

    et al. Engineered riboregulators enable post-transcriptional control of gene expression. Nature Biotech. 22, 841–847 (2004).

  87. 87.

    , , & Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol. Syst. Biol. 3, 91 (2007).

  88. 88.

    , , , & A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130, 797–810 (2007).

  89. 89.

    , , , & Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death. Cell 135, 679–690 (2008).

  90. 90.

    et al. A synthetic mammalian gene circuit reveals antituberculosis compounds. Proc. Natl Acad. Sci. USA 105, 9994–9998 (2008).

  91. 91.

    & Dispersing biofilms with engineered enzymatic bacteriophage. Proc. Natl Acad. Sci. USA 104, 11197–11202 (2007).

  92. 92.

    & Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. Proc. Natl Acad. Sci. USA 106, 4629–4634 (2009). In references 91 and 92, engineered bacteriophages were used to deliver synthetic enzymes and perturb gene networks to combat antibiotic-resistant strains of bacteria.

  93. 93.

    et al. Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy. Nature Biotech. 19, 1035–1041 (2001).

  94. 94.

    , , & Environmentally controlled invasion of cancer cells by engineered bacteria. J. Mol. Biol. 355, 619–627 (2006). This study provides a potential synthetic approach to cancer therapy. Bacteria were programmed to sense environmental cues of the tumour microenvironment and respond to them by invading malignant cells.

  95. 95.

    et al. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nature Cell Biol. 11, 1093–1102 (2009).

  96. 96.

    et al. A synthetic time-delay circuit in mammalian cells and mice. Proc. Natl Acad. Sci. USA 104, 2643–2648 (2007).

  97. 97.

    et al. Resistance to diet-induced obesity in mice with synthetic glyoxylate shunt. Cell Metab. 9, 525–536 (2009).

  98. 98.

    et al. Biofuel alternatives to ethanol: pumping the microbial well. Trends Biotechnol. 26, 375–381 (2008).

  99. 99.

    & Engineering for biofuels: exploiting innate microbial capacity or importing biosynthetic potential? Nature Rev. Microbiol. 7, 715–723 (2009).

  100. 100.

    & Acetone-butanol fermentation revisited. Microbiol. Rev. 50, 484–524 (1986).

  101. 101.

    , & Design of antisense RNA constructs for downregulation of the acetone formation pathway of Clostridium acetobutylicum. J. Bacteriol. 185, 1923–1934 (2003).

  102. 102.

    et al. Targeted gene disruption by use of a group II intron (targetron) vector in Clostridium acetobutylicum. Cell Res. 17, 963–965 (2007).

  103. 103.

    et al. Expression of Clostridium acetobutylicum butanol synthetic genes in Escherichia coli. Appl. Microbiol. Biotechnol. 77, 1305–1316 (2008).

  104. 104.

    , & Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature 451, 86–89 (2008).

  105. 105.

    , , , & Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nature Biotech. 21, 796–802 (2003).

  106. 106.

    et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440, 940–943 (2006). References 105 and 106 provide a paradigm for the application of synthetic biology to the construction and optimization of biosynthetic pathways for cost-effective and high-yield microbial production. In these papers, the authors demonstrate industrial production of the direct precursor to the antimalarial drug artemisinin as part of a broader effort to address worldwide shortages of rare drugs.

  107. 107.

    et al. Microbial production of fatty-acid-derived fuels and chemicals from plant biomass. Nature 463, 559–562 (2010).

  108. 108.

    et al. Synthesis of methyl halides from biomass using engineered microbes. J. Am. Chem. Soc. 131, 6508–6515 (2009).

  109. 109.

    et al. Complete reconstitution of a highly reducing iterative polyketide synthase. Science 326, 589–592 (2009).

  110. 110.

    et al. Total synthesis of long DNA sequences: synthesis of a contiguous 32-kb polyketide synthase gene cluster. Proc. Natl Acad. Sci. USA 101, 15573–15578 (2004).

  111. 111.

    , , & Tuning genetic control through promoter engineering. Proc. Natl Acad. Sci. USA 102, 12678–12683 (2005).

  112. 112.

    , & Diversity-based, model-guided construction of synthetic gene networks with predicted functions. Nature Biotech. 27, 465–471 (2009).

  113. 113.

    , & Next-generation synthetic gene networks. Nature Biotech. 27, 1139–1150 (2009).

  114. 114.

    Genetic parts to program bacteria. Curr. Opin. Biotechnol. 17, 548–557 (2006).

  115. 115.

    et al. Engineering the Salmonella type III secretion system to export spider silk monomers. Mol. Syst. Biol. 5, 309 (2009).

  116. 116.

    et al. Adaptive prediction of environmental changes by microorganisms. Nature 460, 220–224 (2009).

  117. 117.

    , & Predictive behavior within microbial genetic networks. Science 320, 1313–1317 (2008).

  118. 118.

    et al. Molecular circuits for associative learning in single-celled organisms. J. R. Soc. Interface 6, 463–469 (2009).

  119. 119.

    , , & Designing sequential transcription logic: a simple genetic circuit for conditional memory. Syst. Synth. Biol. 1, 89–98 (2007).

  120. 120.

    Molecular bases for circadian clocks. Cell 96, 271–290 (1999).

  121. 121.

    et al. Programming cells by multiplex genome engineering and accelerated evolution. Nature 460, 894–898 (2009). Provides a combinatorial/evolutionary approach to optimizing biosynthetic pathway components through rapid in vivo genome engineering by cycles of targeted genome modification and phenotype selection.

  122. 122.

    , , & Noise in eukaryotic gene expression. Nature 422, 633–637 (2003).

  123. 123.

    et al. A bottom-up approach to gene regulation. Nature 439, 856–860 (2006).

  124. 124.

    , & Automated design of synthetic ribosome binding sites to control protein expression. Nature Biotech. 27, 946–950 (2009).

  125. 125.

    et al. Synthetic protein scaffolds provide modular control over metabolic flux. Nature Biotech. 27, 753–759 (2009).

  126. 126.

    et al. Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science 319, 1215–1220 (2008).

  127. 127.

    et al. Essential genes of a minimal bacterium. Proc. Natl Acad. Sci. USA 103, 425–430 (2006).

  128. 128.

    et al. Genome transplantation in bacteria: changing one species to another. Science 317, 632–638 (2007).

  129. 129.

    et al. Creating bacterial strains from genomes that have been cloned and engineered in yeast. Science 325, 1693–1696 (2009).

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Acknowledgements

We thank members of the Collins laboratory for helpful discussions and K. M. Flynn for help with artwork. We also thank the Howard Hughes Medical Institute and the US National Institutes of Health Director's Pioneer Award Program for their financial support.

Author information

Affiliations

  1. Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for BioDynamics and Center for Advanced Biotechnology, Boston University, Boston, Massachusetts 02215, USA.

    • Ahmad S. Khalil
    •  & James J. Collins

  2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.

    • James J. Collins

Authors

  1. Search for Ahmad S. Khalil in:

  2. Search for James J. Collins in:

Competing interests

Ahmad S. Khalil and James J. Collins hold various patents and/or patent applications related to the applications of synthetic biology that are discussed in this Review.

Corresponding author

Correspondence to James J. Collins.

Glossary

Memory elements

Devices used to store information about the current state of a system.

Pulse generators

Circuits or devices used to generate pulses. A biological pulse generator has been implemented in a multicellular bacterial system, in which receiver cells respond to a chemical signal with a transient burst of gene expression, the amplitude and duration of which depends on the distance from the sender cells.

Digital logic gates

A digital logic gate implements Boolean logic (such as AND, OR or NOT) on one or more logic inputs to produce a single logic output. Electronic logic gates are implemented using diodes and transistors and operate on input voltages or currents, whereas biological logic gates operate on cellular molecules (chemical or biological).

Filters

Algorithms or devices for removing or enhancing parts or frequency components from a signal.

Modularity

The capacity of a system or component to function independently of context.

Environment-responsive promoters

Promoters that directly transduce environmental signals (for example, heavy metal ions, hormones, chemicals or temperature) that are captured by their associated sensory transcription factors.

Quorum sensing

A cell-to-cell communication mechanism in many species of bacteria, whereby cells measure their local density (by the accumulation of a signalling molecule) and subsequently coordinate gene expression.

NOR gate

A digital logic gate that implements logical NOR, or the negation of the OR operator. It produces a HIGH output (1) only if both inputs to the gate are LOW (0).

Aptamer

Oligonucleic acids that bind to a specific target molecule, such as a small molecule, protein or nucleic acid. Nucleic acid aptamers are typically developed through in vitro selection schemes but are also found naturally (for example, RNA aptamers in riboswitches).

Antisense RNAs

RNAs that bind segments of mRNA in trans to inhibit translation.

Riboregulators

Small regulatory RNAs that can activate or repress gene expression by binding segments of mRNA in trans. They are typically expressed in response to an environmental signalling event.

Two-component systems

Among the simplest types of signal transduction pathways. In bacteria, they consist of two domains: a membrane-bound histidine kinase (sensitive element) that senses a specific environmental stimulus, and a cognate response regulator (transducer domain) that triggers a cellular response.

Orthogonal environment

A cellular environment or host into which genetic material is transplanted to avoid undesired native host interference or regulation. Orthogonal hosts are often organisms with sufficient evolutionary distance from the native host.

DNA gyrase

A type II DNA topoisomerase that catalyses the ATP-dependent supercoiling of closed-circular dsDNA by strand breakage and rejoining reactions. Control of chromosomal topological transitions is essential for DNA replication and transcription in bacteria, making gyrase an effective target for antimicrobial agents (for example, the quinolone class of antibiotics).

Biofilms

Surface-associated communities of bacterial cells encapsulated in an extracellular polymeric substances (EPS) matrix. Biofilms are an antibiotic-resistant mode of microbial life found in natural and industrial settings.

Ultradian

Periods or cycles that are repeated throughout a 24-hour circadian day.

Glyoxylate shunt pathway

A two-enzyme metabolic pathway unique to bacteria and plants that is activated when sugars are not readily available. This pathway diverts the tricarboxylic acid (TCA) cycle so that fatty acids are not completely oxidized and are instead converted into carbon energy sources.

Metabolic flux

The rate of flow of metabolites through a metabolic pathway. The rate is regulated by the enzymes in the pathway.

Flocculation

A specific form of cell aggregation in yeast triggered by certain environmental conditions, such as the absence of sugars. For example, flocculation occurs once the sugar in a beer brew has been fermented into ethanol.

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