Abstract
Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Cameron DE, Bashor CJ, Collins JJ. A brief history of synthetic biology. Nat Rev Microbiol, 2014, 12: 381–390
Chao R, Yuan Y, Zhao H. Recent advances in DNA assembly technologies. FEMS Yeast Res, 2015, 15: 1–9
Shetty RP, Endy D, Knight TF, Jr. Engineering biobrick vectors from biobrick parts. J Biol Eng, 2008, 2: 5
Partregistry. Registry of standard biological parts. 2014, http://www.webcitation.org/6O8Ha2b2B
Elowitz MB, Levine AJ, Siggia ED, Swain PS. Stochastic gene expression in a single cell. Science, 2002, 297: 1183–1186
Blake WJ, KÆrn M, Cantor CR, Collins JJ. Noise in eukaryotic gene expression. Nature, 2003, 422: 633–637
Luo YZ, Huang H, Liang J, Wang M, Lu L, Shao ZY, Cobb RE, Zhao HM. Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster. Nat Commun, 2013, 4: 2894
Yamanaka K, Reynolds KA, Kersten RD, Ryan KS, Gonzalez DJ, Nizet V, Dorrestein PC, Moore BS. Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin a. Proc Natl Acad Sci USA, 2014, 111: 1957–1962
Warner JR, Reeder PJ, Karimpour-Fard A, Woodruff LBA, Gill RT. Rapid profiling of a microbial genome using mixtures of barcoded oligonucleotides. Nat Biotechnol, 2010, 28: 856–862
Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, Hsu PD, Wu XB, Jiang WY, Marraffini LA, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science, 2013, 339: 819–823
Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Jiang H, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD. High-level semi-synthetic production of the potent antimalarial artemisinin. Nature, 2013, 496: 528–532
Holtz WJ, Keasling JD. Engineering static and dynamic control of synthetic pathways. Cell, 2010, 140: 19–23
Anderson JC, Clarke EJ, Arkin AP, Voigt CA. Environmentally controlled invasion of cancer cells by engineered bacteria. J Mol Biol, 2006, 355: 619–627
Zhang F, Carothers JM, Keasling JD. Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat Biotechnol, 2012, 30: 354–359
Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM. Programming cells by multiplex genome engineering and accelerated evolution. Nature, 2009, 460: 894–898
Jiang WY, Bikard D, Cox D, Zhang F, Marraffini LA. RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol, 2013, 31: 233–239
Bao Z, Xiao H, Liang J, Zhang L, Xiong X, Sun N, Si T, Zhao H. Homology-integrated CRISPR-Cas (HI-CRISPR) system for one-step multigene disruption in Saccharomyces cerevisiae. ACS Synth Biol, 2014, doi: 10.1021/sb500255k
Gardner TS, Cantor CR, Collins JJ. Construction of a genetic toggle switch in Escherichia coli. Nature, 2000, 403: 339–342
Elowitz MB, Leibler S. A synthetic oscillatory network of transcriptional regulators. Nature, 2000, 403: 335–338
Guet CC, Elowitz MB, Hsing W, Leibler S. Combinatorial synthesis of genetic networks. Science, 2002, 296: 1466–1470
Baker D, Group BF, Church G, Collins J, Endy D, Jacobson J, Keasling J, Modrich P, Smolke C, Weiss R. Engineering life: building a fab for biology. Sci Am, 2006, 294: 44–51
Kim B, Du J, Eriksen DT, Zhao HM. Combinatorial design of a highly efficient xylose-utilizing pathway in Saccharomyces cerevisiae for the production of cellulosic biofuels. Appl Environ Microb, 2013, 79: 931–941
Shao ZY, Zhao H, Zhao HM. DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res, 2009, 37: e16
Salis HM, Mirsky EA, Voigt CA. Automated design of synthetic ribosome binding sites to control protein expression. Nat Biotechnol, 2009, 27: 946–950
Curran KA, Crook NC, Karim AS, Gupta A, Wagman AM, Alper HS. Design of synthetic yeast promoters via tuning of nucleosome architecture. Nat Commun, 2014, 5: 4002
MacDonald JT, Barnes C, Kitney RI, Freemont PS, Stan GB. Computational design approaches and tools for synthetic biology. Integr Biol (Camb), 2011, 3: 97–108
Brophy JA, Voigt CA. Principles of genetic circuit design. Nat Methods, 2014, 11: 508–520
Lewis NE, Nagarajan H, Palsson BO. Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods. Nat Rev Microbiol, 2012, 10: 291–305
Prather KL, Martin CH. De novo biosynthetic pathways: rational design of microbial chemical factories. Curr Opin Biotechnol, 2008, 19: 468–474
Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M. The kegg resource for deciphering the genome. Nucleic Acids Res, 2004, 32: D277–280
Ellis LBM, Roe D, Wackett LP. The University of Minnesota biocatalysis/biodegradation database: the first decade. Nucleic Acids Res, 2006, 34: D517–521
Schomburg I, Chang A, Schomburg D. Standardization in enzymology—data integration in the world’s enzyme information system brenda. Persp Sci, 2014, 1: 15–23
Hatzimanikatis V, Li C, Ionita JA, Henry CS, Jankowski MD, Broadbelt LJ. Exploring the diversity of complex metabolic networks. Bioinformatics, 2005, 21: 1603–1609
Gonzalez-Lergier J, Broadbelt LJ, Hatzimanikatis V. Theoretical considerations and computational analysis of the complexity in polyketide synthesis pathways. J Am Chem Soc, 2005, 127: 9930–9938
Hou BK, Ellis LB, Wackett LP. Encoding microbial metabolic logic: predicting biodegradation. J Ind Microbiol Biotechnol, 2004, 31: 261–272
Lu G, Moriyama EN. Vector NTI, a balanced all-in-one sequence analysis suite. Brief Bioinform, 2004, 5: 378–388
Hillson NJ, Rosengarten RD, Keasling JD. J5 DNA assembly design automation software. ACS Synth Biol, 2012, 1: 14–21
Appleton E, Tao JH, Haddock T, Densmore D. Interactive assembly algorithms for molecular cloning. Nat Methods, 2014, 11: 657–662
Ellis T, Adie T, Baldwin GS. DNA assembly for synthetic biology: from parts to pathways and beyond. Integr Biol (Camb), 2011, 3: 109–118
McLennan A. Building with Biobricks: Constructing a Commons for Synthetic Biology Research. Cheltenham: Edward Elgar, 2012. 176–201
Grünberg R, Arndt K, Müller K. Fusion protein (freiburg) biobrick assembly standard [OL]. [2009-04-18]. http://hdl.handle.net/1721.1/45140
Phillips I, Silver P. A new biobrick assembly strategy designed for facile protein engineering [OL]. [2006-04-20]. http://hdl.handle.net/1721.1/32535
Anderson JC, Dueber JE, Leguia M, Wu GC, Goler JA, Arkin AP, Keasling JD. Bglbricks: A flexible standard for biological part assembly. J Biol Eng, 2010, 4: 1
Engler C, Kandzia R, Marillonnet S. A one pot, one step, precision cloning method with high throughput capability. PLoS One, 2008, 3: e3647
Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith HO. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods, 2009, 6: 343–345
Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA, 3rd, Smith HO. Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science, 2008, 319: 1215–1220
Itaya M, Fujita K, Kuroki A, Tsuge K. Bottom-up genome assembly using the Bacillus subtilis genome vector. Nat Methods, 2008, 5: 41–43
Yonemura I, Nakada K, Sato A, Hayashi JI, Fujita K, Kaneko S, Itaya M. Direct cloning of full-length mouse mitochondrial DNA using a Bacillus subtilis genome vector. Gene, 2007, 391: 171–177
Zhu CF, Naqvi S, Breitenbach J, Sandmann G, Christou P, Capell T. Combinatorial genetic transformation generates a library of metabolic phenotypes for the carotenoid pathway in maize. Proc Natl Acad Sci USA, 2008, 105: 18232–18237
Farre G, Naqvi S, Sanahuja G, Bai C, Zorrilla-Lopez U, Rivera SM, Canela R, Sandman G, Twyman RM, Capell T, Zhu CF, Christou P. Combinatorial genetic transformation of cereals and the creation of metabolic libraries for the carotenoid pathway. Trans Plants Methods Mol Biol, 2012, 847: 419–435
Zhang YM, Muyrers JPP, Testa G, Stewart AF. DNA cloning by homologous recombination in Escherichia coli. Nat Biotechnol, 2000, 18: 1314–1317
Fu J, Bian XY, Hu SB, Wang HL, Huang F, Seibert PM, Plaza A, Xia LQ, Muller R, Stewart AF, Zhang YM. Full-length rece enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting. Nat Biotechnol, 2012, 30: 440–446
Pachuk CJ, Samuel M, Zurawski JA, Snyder L, Phillips P, Satishchandran C. Chain reaction cloning: a one-step method for directional ligation of multiple DNA fragments. Gene, 2000, 243: 19–25
De Kok S, Stanton LH, Slaby T, Durot M, Holmes VF, Patel KG, Platt D, Shapland EB, Serber Z, Dean J, Newman JD, Chandran SS. Rapid and reliable DNA assembly via ligase cycling reaction. Acs Synth Biol, 2014, 3: 97–106
Wingler LM, Cornish VW. Reiterative recombination for the in vivo assembly of libraries of multigene pathways. Proc Natl Acad Sci USA, 2011, 108: 15135–15140
Anderson PR, Haj-Ahmad Y. Counter-selection facilitated plasmid construction by homologous recombination in saccharomyces cerevisiae. Biotechniques, 2003, 35: 692–694
Kuijpers NG, Solis-Escalante D, Bosman L, van den Broek M, Pronk JT, Daran JM, Daran-Lapujade P. A versatile, efficient strategy for assembly of multi-fragment expression vectors in saccharomyces cerevisiae using 60 bp synthetic recombination sequences. Microb Cell Fact, 2013, 12: 47
Liang J, Chao R, Abil Z, Bao Z, Zhao H. Fairytale: a high-throughput tal effector synthesis platform. ACS Synth Biol, 2014, 3: 67–73
Guye P, Li Y, Wroblewska L, Duportet X, Weiss R. Rapid, modular and reliable construction of complex mammalian gene circuits. Nucleic Acids Res, 2013, 41: e156
Torella JP, Boehm CR, Lienert F, Chen JH, Way JC, Silver PA. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly. Nucleic Acids Res, 2014, 42: 681–689
Casini A, MacDonald JT, De Jonghe J, Christodoulou G, Freemont PS, Baldwin GS, Ellis T. One-pot DNA construction for synthetic biology: the modular overlap-directed assembly with linkers (modal) strategy. Nucleic Acids Res, 2014, 42: e7
Kosuri S, Church GM. Large-scale de novo DNA synthesis: technologies and applications. Nat Methods, 2014, 11: 499–507
Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA, Smith HO. Complete chemical synthesis, assembly, and cloning of a mycoplasma genitalium genome. Science, 2008, 319: 1215–1220
Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, Smith HO, Venter JC. Creation of a bacterial cell controlled by a chemically synthesized genome. Science, 2010, 329: 52–56
Annaluru N, Muller H, Mitchell LA, Ramalingam S, Stracquadanio G, Richardson SM, Dymond JS, Kuang Z, Scheifele LZ, Cooper EM, Cai Y, Zeller K, Agmon N, Han JS, Hadjithomas M, Tullman J, Caravelli K, Cirelli K, Guo Z, London V, Yeluru A, Murugan S, Kandavelou K, Agier N, Fischer G, Yang K, Martin JA, Bilgel M, Bohutski P, Boulier KM, Capaldo BJ, Chang J, Charoen K, Choi WJ, Deng P, DiCarlo JE, Doong J, Dunn J, Feinberg JI, Fernandez C, Floria CE, Gladowski D, Hadidi P, Ishizuka I, Jabbari J, Lau CY, Lee PA, Li S, Lin D, Linder ME, Ling J, Liu J, London M, Ma H, Mao J, McDade JE, McMillan A, Moore AM, Oh WC, Ouyang Y, Patel R, Paul M, Paulsen LC, Qiu J, Rhee A, Rubashkin MG, Soh IY, Sotuyo NE, Srinivas V, Suarez A, Wong A, Wong R, Xie WR, Xu Y, Yu AT, Koszul R, Bader JS, Boeke JD, Chandrasegaran S. Total synthesis of a functional designer eukaryotic chromosome. Science, 2014, 344: 55–58
Dharmadi Y, Patel K, Shapland E, Hollis D, Slaby T, Klinkner N, Dean J, Chandran SS. High-throughput, cost-effective verification of structural DNA assembly. Nucleic Acids Res, 2014, 42: e22
Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet, 2010, 11: 31–46
Coen M, Holmes E, Lindon JC, Nicholson JK. NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chem Res Toxicol, 2008, 21: 9–27
Fiehn O. Extending the breadth of metabolite profiling by gas chromatography coupled to mass spectrometry. Trac-Trend Anal Chem, 2008, 27: 261–269
Khakimov B, Motawia MS, Bak S, Engelsen SB. The use of trimethylsilyl cyanide derivatization for robust and broad-spectrum high-throughput gas chromatography-mass spectrometry based metabolomics. Anal Bioanal Chem, 2013, 405: 9193–9205
Allwood JW, Goodacre R. An introduction to liquid chromatography-mass spectrometry instrumentation applied in plant metabolomic analyses. Phytochem Anal, 2010, 21: 33–47
Mischak H, Coon JJ, Novak J, Weissinger EM, Schanstra JP, Dominiczak AF. Capillary electrophoresis-mass spectrometry as a powerful tool in biomarker discovery and clinical diagnosis: an update of recent developments. Mass Spectrom Rev, 2009, 28: 703–724
Lapainis T, Rubakhin SS, Sweedler JV. Capillary electrophoresis with electrospray ionization mass spectrometric detection for single-cell metabolomics. Anal Chem, 2009, 81: 5858–5864
Khakimov B, Bak S, Engelsen SB. High-throughput cereal metabolomics: current analytical technologies, challenges and perspectives. J Cereal Sci, 2014, 59: 393–418
Yukihira D, Miura D, Saito K, Takahashi K, Wariishi H. MALDI-MS-based high-throughput metabolite analysis for intracellular metabolic dynamics. Anal Chem, 2010, 82: 4278–4282
Vaidyanathan S, Goodacre R. Quantitative detection of metabolites using matrix-assisted laser desorption/ionization mass spectrometry with 9-aminoacridine as the matrix. Rapid Commun Mass Spectrom, 2007, 21: 2072–2078
Yanes O. Metabolomics playing pinata with single cells. Nat Chem Biol, 2013, 9: 471–473
Rubakhin SS, Romanova EV, Nemes P, Sweedler JV. Profiling metabolites and peptides in single cells. Nat Methods, 2011, 8: S20–29
Author information
Authors and Affiliations
Corresponding author
Additional information
Contributed equally to this work
This article is published with open access at springerlink.fh-diploma.de
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Chao, R., Yuan, Y. & Zhao, H. Building biological foundries for next-generation synthetic biology. Sci. China Life Sci. 58, 658–665 (2015). https://doi.org/10.1007/s11427-015-4866-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-015-4866-8