A perspective of synthetic biology: Assembling building blocks for novel functions

Synthetic biology is a recently emerging field that applies engineering formalisms to design and construct new biological parts, devices, and systems for novel functions or life forms that do not exist in nature. Synthetic biology relies on and shares tools from genetic engineering, bioengineering, systems biology and many other engineering disciplines. It is also different from these subjects, in both insights and approach. Applications of synthetic biology have great potential for novel contributions to established fields and for offering opportunities to answer fundamentally new biological questions. This article does not aim at a thorough survey of the literature and detailing progress in all different directions. Instead, it is intended to communicate a way of thinking for synthetic biology in which basic functional elements are defined and assembled into living systems or biomaterials with new properties and behaviors. Four major application areas with a common theme are discussed and a procedure (or “protocol”) for a standard synthetic biology work is suggested.

[1]  Satoru Miyano,et al.  Estimation of Genetic Networks and Functional Structures Between Genes by Using Bayesian Networks and Nonparametric Regression , 2001, Pacific Symposium on Biocomputing.

[2]  Carlo D. Montemagno,et al.  Nanomachines: A Roadmap for Realizing the Vision , 2001 .

[3]  Martin Rosenberg,et al.  Identification of Critical Staphylococcal Genes Using Conditional Phenotypes Generated by Antisense RNA , 2001, Science.

[4]  Kazuhiko Kinosita,et al.  F1-ATPase Is a Highly Efficient Molecular Motor that Rotates with Discrete 120° Steps , 1998, Cell.

[5]  M. Elowitz,et al.  Modeling a synthetic multicellular clock: repressilators coupled by quorum sensing. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Wolf,et al.  On the relationship between genomic regulatory element organization and gene regulatory dynamics. , 1998, Journal of theoretical biology.

[7]  D. Bray Molecular Networks: The Top-Down View , 2003, Science.

[8]  A. C. Chang,et al.  Construction of biologically functional bacterial plasmids in vitro. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Ron Weiss,et al.  Genetic circuit building blocks for cellular computation, communications, and signal processing , 2003, Natural Computing.

[10]  Michael L Simpson,et al.  Rewiring the cell: synthetic biology moves towards higher functional complexity. , 2004, Trends in biotechnology.

[11]  Savageau Ma Rules for the evolution of gene circuitry. , 1998 .

[12]  P. Boyer The ATP synthase--a splendid molecular machine. , 1997, Annual review of biochemistry.

[13]  R. Milo,et al.  Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  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.

[15]  Jan Pieter Abrahams,et al.  Structure at 2.8 Â resolution of F1-ATPase from bovine heart mitochondria , 1994, Nature.

[16]  S. Block Real engines of creation , 1997, Nature.

[17]  Kazuhiko Kinosita,et al.  Direct observation of the rotation of F1-ATPase , 1997, Nature.

[18]  M. Sisido,et al.  Five-base codons for incorporation of nonnatural amino acids into proteins. , 2001, Nucleic acids research.

[19]  Ron Weiss,et al.  Evolutionary Design of Genetic Circuits and Cell-Cell Communications , 2003, Adv. Complex Syst..

[20]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[21]  N. Packard,et al.  Transitions from Nonliving to Living Matter , 2004, Science.

[22]  H. McAdams,et al.  Gene regulation: Towards a circuit engineering discipline , 2000, Current Biology.

[23]  Viola Vogel,et al.  Molecular shuttles: directed motion of microtubules along nanoscale kinesin tracks , 1999 .

[24]  Michael P. Sheetz,et al.  Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility , 1985, Cell.

[25]  B. Bassler,et al.  Quorum sensing in bacteria. , 2001, Annual review of microbiology.

[26]  Hidde de Jong,et al.  Qualitative Simulation of Large and Complex Genetic Regulation Systems , 2000, ECAI.

[27]  P. Karp,et al.  Computational prediction of human metabolic pathways from the complete human genome , 2004, Genome Biology.

[28]  Andrew B. Martin,et al.  Generation of a bacterium with a 21 amino acid genetic code. , 2003, Journal of the American Chemical Society.

[29]  C. J. Noren,et al.  In vitro suppression of an amber mutation by a chemically aminoacylated transfer RNA prepared by runoff transcription , 1990, Nucleic Acids Res..

[30]  P. Schultz,et al.  The use of 5'-phospho-2 deoxyribocytidylylriboadenosine as a facile route to chemical aminoacylation of tRNA. , 1989, Nucleic acids research.

[31]  H. Craighead,et al.  Powering an inorganic nanodevice with a biomolecular motor. , 2000, Science.

[32]  Pier Luigi Luisi,et al.  The Notion of a DNA Minimal Cell: A General Discourse and Some Guidelines for an Experimental Approach , 2002 .

[33]  H. Westerhoff,et al.  Building the cellular puzzle: control in multi-level reaction networks. , 2001, Journal of theoretical biology.

[34]  Roger Brent,et al.  A partnership between biology and engineering , 2004, Nature Biotechnology.

[35]  U. Alon,et al.  Negative autoregulation speeds the response times of transcription networks. , 2002, Journal of molecular biology.

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

[37]  M. Wall,et al.  Design of gene circuits: lessons from bacteria , 2004, Nature Reviews Genetics.

[38]  P. Brazhnik,et al.  Gene networks: how to put the function in genomics. , 2002, Trends in biotechnology.

[39]  J Craig Venter,et al.  Generating a synthetic genome by whole genome assembly: φX174 bacteriophage from synthetic oligonucleotides , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[40]  P. Swain,et al.  Stochastic Gene Expression in a Single Cell , 2002, Science.

[41]  Satoru Miyano,et al.  Identification of Genetic Networks from a Small Number of Gene Expression Patterns Under the Boolean Network Model , 1998, Pacific Symposium on Biocomputing.

[42]  S. Basu,et al.  Spatiotemporal control of gene expression with pulse-generating networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  U. Alon Biological Networks: The Tinkerer as an Engineer , 2003, Science.

[44]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[45]  Joel L Cuello The descent of Biological Engineering , 2006 .

[46]  Roland Stracke,et al.  Motor protein-driven unidirectional transport of micrometer-sized cargoes across isopolar microtubule arrays , 2001 .

[47]  Jeffrey M. Perkel Investigating molecular motors step by step , 2004 .

[48]  Hong-Yu Ou,et al.  EG: a database of essential genes , 2004, Nucleic Acids Res..

[49]  John Sullins Synthetic Biology: The Technoscience of Artificial Life , 1998 .

[50]  J. Monod,et al.  Genetic regulatory mechanisms in the synthesis of proteins. , 1961, Journal of molecular biology.

[51]  E V Koonin,et al.  How many genes can make a cell: the minimal-gene-set concept. , 2000, Annual review of genomics and human genetics.

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

[53]  Norbert Wiener,et al.  Cybernetics: Control and Communication in the Animal and the Machine. , 1949 .

[54]  Jacob J. Schmidt,et al.  Engineering Issues in the Fabrication of a Hybrid Nano-Propeller System Powered by F1-ATPase , 2001 .

[55]  Nicola J. Rinaldi,et al.  Computational discovery of gene modules and regulatory networks , 2003, Nature Biotechnology.

[56]  Michael P. Sheetz,et al.  A model for kinesin movement from nanometer-level movements of kinesin and cytoplasmic dynein and force measurements , 1991, Journal of Cell Science.

[57]  A. Paul,et al.  Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template , 2002, Science.

[58]  A. Ninfa,et al.  Development of Genetic Circuitry Exhibiting Toggle Switch or Oscillatory Behavior in Escherichia coli , 2003, Cell.

[59]  A. Rinaldi A new code for life , 2004, EMBO reports.

[60]  Arthur L. Caplan,et al.  Policy forum: genetics. Ethical considerations in synthesizing a minimal genome. , 1999, Science.

[61]  M. Sisido,et al.  Incorporation of nonnatural amino acids into proteins by using various four-base codons in an Escherichia coli in vitro translation system. , 2001, Biochemistry.

[62]  D. Deamer,et al.  A giant step towards artificial life? , 2005, Trends in biotechnology.

[63]  Brian O. Bachmann,et al.  A genomics-guided approach for discovering and expressing cryptic metabolic pathways , 2003, Nature Biotechnology.

[64]  S Fuhrman,et al.  Reveal, a general reverse engineering algorithm for inference of genetic network architectures. , 1998, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[65]  P. Schultz,et al.  Expanding the Genetic Code , 2003, Science.

[66]  Peter G Schultz,et al.  An Expanded Eukaryotic Genetic Code , 2003, Science.

[67]  P. Swain,et al.  Intrinsic and extrinsic contributions to stochasticity in gene expression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[68]  J. Howard,et al.  Inhibition of kinesin motility by ADP and phosphate supports a hand-over-hand mechanism. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Manuel Peitsch,et al.  A genome-based approach for the identification of essential bacterial genes , 1998, Nature Biotechnology.

[70]  S. Ehrlich,et al.  Essential Bacillus subtilis genes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[71]  J. Collins,et al.  Inferring Genetic Networks and Identifying Compound Mode of Action via Expression Profiling , 2003, Science.

[72]  P. Schultz,et al.  Addition of the keto functional group to the genetic code of Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[73]  E. Koonin,et al.  A minimal gene set for cellular life derived by comparison of complete bacterial genomes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Steven E. Brenner,et al.  Computational Structural Genomics of a Complete Minimal Organism , 2002 .

[75]  Loren L Looger,et al.  Control of a biomolecular motor-powered nanodevice with an engineered chemical switch , 2002, Nature materials.

[76]  O. White,et al.  Global transposon mutagenesis and a minimal Mycoplasma genome. , 1999, Science.

[77]  V. V. Bulygin,et al.  Rotation of subunits during catalysis by Escherichia coli F1-ATPase. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[78]  Eric H Davidson,et al.  A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo. , 2002, Developmental biology.

[79]  Bartholomew Canton,et al.  Engineering the Interface Between Cellular Chassis and Integrated Biological Systems , 2005 .

[80]  M Wahde,et al.  Coarse-grained reverse engineering of genetic regulatory networks. , 2000, Bio Systems.

[81]  Mads Kaern,et al.  The engineering of gene regulatory networks. , 2003, Annual review of biomedical engineering.

[82]  B O Palsson,et al.  Metabolic modeling of microbial strains in silico. , 2001, Trends in biochemical sciences.