Systematic Biological Filter Design with a Desired I/O Filtering Response Based on Promoter-RBS Libraries

In this study, robust biological filters with an external control to match a desired input/output (I/O) filtering response are engineered based on the well-characterized promoter-RBS libraries and a cascade gene circuit topology. In the field of synthetic biology, the biological filter system serves as a powerful detector or sensor to sense different molecular signals and produces a specific output response only if the concentration of the input molecular signal is higher or lower than a specified threshold. The proposed systematic design method of robust biological filters is summarized into three steps. Firstly, several well-characterized promoter-RBS libraries are established for biological filter design by identifying and collecting the quantitative and qualitative characteristics of their promoter-RBS components via nonlinear parameter estimation method. Then, the topology of synthetic biological filter is decomposed into three cascade gene regulatory modules, and an appropriate promoter-RBS library is selected for each module to achieve the desired I/O specification of a biological filter. Finally, based on the proposed systematic method, a robust externally tunable biological filter is engineered by searching the promoter-RBS component libraries and a control inducer concentration library to achieve the optimal reference match for the specified I/O filtering response.

[1]  Adam Arkin,et al.  Setting the standard in synthetic biology , 2008, Nature Biotechnology.

[2]  Alfonso Jaramillo,et al.  Computational design of synthetic regulatory networks from a genetic library to characterize the designability of dynamical behaviors , 2011, Nucleic acids research.

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

[4]  John J. Grefenstette,et al.  Optimization of Control Parameters for Genetic Algorithms , 1986, IEEE Transactions on Systems, Man, and Cybernetics.

[5]  Chun-Liang Lin,et al.  A Novel Synthesizing Genetic Logic Circuit: Frequency Multiplier , 2014, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[6]  Yiannis N Kaznessis,et al.  Model-driven designs of an oscillating gene network. , 2005, Biophysical journal.

[7]  Timothy K Lu,et al.  Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy , 2009, Proceedings of the National Academy of Sciences.

[8]  R. Weiss,et al.  Cancer Cells Multi-Input RNAi-Based Logic Circuit for Identification of Specific , 2011 .

[9]  T. Cao,et al.  Logic Gates and Computation from Assembled Nanowire Building Blocks , 2001 .

[10]  Christopher A. Voigt,et al.  Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’ , 2011, Nature.

[11]  Jacob Beal,et al.  An end-to-end workflow for engineering of biological networks from high-level specifications. , 2012, ACS synthetic biology.

[12]  Bor-Sen Chen,et al.  Robust synthetic gene network design via library-based search method , 2011, Bioinform..

[13]  C. Townsend,et al.  An externally tunable bacterial band-pass filter , 2009, Proceedings of the National Academy of Sciences.

[14]  Ryan T Gill,et al.  Synthetic biology: new strategies for directing design. , 2012, Metabolic engineering.

[15]  D. Endy.  Foundations for engineering biology , 2005, Nature.

[16]  Martin Fussenegger,et al.  Rewiring and dosing of systems modules as a design approach for synthetic mammalian signaling networks. , 2012, Molecular bioSystems.

[17]  Herbert M. Sauro,et al.  Design and implementation of three incoherent feed-forward motif based biological concentration sensors , 2007, Systems and Synthetic Biology.

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

[19]  Matthias Köppe,et al.  Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming , 2012, PloS one.

[20]  James J. Collins,et al.  Genetic switchboard for synthetic biology applications , 2012, Proceedings of the National Academy of Sciences.

[21]  E. Andrianantoandro,et al.  Synthetic biology: new engineering rules for an emerging discipline , 2006, Molecular systems biology.

[22]  Terence Hwa,et al.  Transcriptional regulation by the numbers: models. , 2005, Current opinion in genetics & development.

[23]  Baojun Wang,et al.  Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology , 2011, Nature communications.

[24]  Timothy S. Ham,et al.  Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels. , 2008, Current opinion in biotechnology.

[25]  Priscilla E. M. Purnick,et al.  The second wave of synthetic biology: from modules to systems , 2009, Nature Reviews Molecular Cell Biology.

[26]  Matthias Köppe,et al.  SBROME: a scalable optimization and module matching framework for automated biosystems design. , 2013, ACS synthetic biology.

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

[28]  Marc Ostermeier,et al.  Morphogen-defined patterning of Escherichia coli enabled by an externally tunable band-pass filter , 2009, Journal of biological engineering.

[29]  Ali Kinkhabwala,et al.  Uncovering cis Regulatory Codes Using Synthetic Promoter Shuffling , 2008, PloS one.

[30]  J. Liao,et al.  Design of artificial cell-cell communication using gene and metabolic networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Drew Endy,et al.  Measuring the activity of BioBrick promoters using an in vivo reference standard , 2009, Journal of biological engineering.

[32]  Goldberg,et al.  Genetic algorithms , 1993, Robust Control Systems with Genetic Algorithms.

[33]  Jay D. Keasling,et al.  Biosynthesis and engineering of isoprenoid small molecules , 2007, Applied Microbiology and Biotechnology.

[34]  Christopher A. Voigt,et al.  Automated design of synthetic ribosome binding sites to control protein expression , 2016 .

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

[36]  Bor-Sen Chen,et al.  Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries , 2013, BMC Systems Biology.

[37]  Bor-Sen Chen,et al.  A genetic approach to mixed H/sub 2//H/sub /spl infin// optimal PID control , 1995 .

[38]  Javier Macía,et al.  Distributed biological computation with multicellular engineered networks , 2011, Nature.

[39]  D. Endy,et al.  Refinement and standardization of synthetic biological parts and devices , 2008, Nature Biotechnology.

[40]  David E. Goldberg,et al.  Genetic Algorithms in Search Optimization and Machine Learning , 1988 .

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

[42]  Pamela A Silver,et al.  Parts plus pipes: synthetic biology approaches to metabolic engineering. , 2012, Metabolic engineering.

[43]  Drew Endy,et al.  Precise and reliable gene expression via standard transcription and translation initiation elements , 2013, Nature Methods.

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

[45]  S. Basu,et al.  A synthetic multicellular system for programmed pattern formation , 2005, Nature.

[46]  J. Keasling.  Synthetic biology and the development of tools for metabolic engineering. , 2012, Metabolic engineering.

[47]  James J. Collins,et al.  Next-Generation Synthetic Gene Networks , 2009, Nature Biotechnology.

[48]  Bor-Sen Chen,et al.  Multiobjective H2/H∞ synthetic gene network design based on promoter libraries. , 2011, Mathematical biosciences.

[49]  Karen M Polizzi.  What is synthetic biology? , 2013, Methods in molecular biology.

[50]  Bor-Sen Chen,et al.  Synthetic Gene Network: Modeling, Analysis and Robust Design Methods , 2014 .