Engineering an allosteric transcription factor to respond to new ligands

Taylor, Noah D.; Garruss, Alexander S.; Moretti, Rocco; Chan, Sum; Arbing, Mark A.; Cascio, Duilio; Rogers, Jameson K.; Isaacs, Farren J.; Kosuri, Sriram; Baker, David; Fields, Stanley; Church, George M.; Raman, Srivatsan

doi:10.1038/nmeth.3696

Title: Engineering an allosteric transcription factor to respond to new ligands

Journal Article · Mon Dec 21 00:00:00 EST 2015 · Nature Methods

DOI:https://doi.org/10.1038/nmeth.3696· OSTI ID:1239401

Taylor, Noah D. ^[1]; Garruss, Alexander S. ^[1]; Moretti, Rocco ^[2]; Chan, Sum ^[3]; Arbing, Mark A. ^[3]; Cascio, Duilio ^[3]; Rogers, Jameson K. ^[1]; Isaacs, Farren J. ^[4];

^[5]; Baker, David ^[2]; Fields, Stanley ^[6]; Church, George M. ^[1]; Raman, Srivatsan ^[1]

Harvard Univ., Boston, MA (United States). Wyss Inst. for Biologically-Inspired Engineering; Harvard Medical School, Boston, MA (United States). Dept. of Genetics
Univ. of Washington, Seattle, WA (United States). Dept. of Biochemistry. Howard Hughes Medical Inst.
Univ. of California, Los Angeles, CA (United States). UCLA-USDOE Inst. for Genomics and Proteomics
Yale Univ., New Haven, CT (United States). Dept. of Molecular, Cellular and Developmental Biology; Yale Univ., West Haven, CT (United States). Systems Biology Inst.
Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry
Univ. of Washington, Seattle, WA (United States). Dept. of Genome Sciences. Dept. of Medicine. Howard Hughes Medical Inst.

Genetic regulatory proteins inducible by small molecules are useful synthetic biology tools as sensors and switches. Bacterial allosteric transcription factors (aTFs) are a major class of regulatory proteins, but few aTFs have been redesigned to respond to new effectors beyond natural aTF-inducer pairs. Altering inducer specificity in these proteins is difficult because substitutions that affect inducer binding may also disrupt allostery. In this paper, we engineered an aTF, the Escherichia coli lac repressor, LacI, to respond to one of four new inducer molecules: fucose, gentiobiose, lactitol and sucralose. Using computational protein design, single-residue saturation mutagenesis or random mutagenesis, along with multiplex assembly, we identified new variants comparable in specificity and induction to wild-type LacI with its inducer, isopropyl β-D-1-thiogalactopyranoside (IPTG). Finally, the ability to create designer aTFs will enable applications including dynamic control of cell metabolism, cell biology and synthetic gene circuits.

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Research Organization:: Harvard Univ., Cambridge, MA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States)

Contributing Organization:: Yale Univ., New Haven, CT (United States); Univ. of California, Los Angeles, CA (United States); Univ. of Washington, Seattle, WA (United States)

Grant/Contract Number:: FG02-02ER63445; FC02-02ER63421; AC02-06CH11357; 1P41 GM103533; P41 RR015301; P41 GM103403

OSTI ID:: 1239401

Journal Information:: Nature Methods, Vol. 13, Issue 2; ISSN 1548-7091

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 198 works

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References (61)

A three-hybrid system for detecting small ligand-protein receptor interactions Licitra, E. J.; Liu, J. O. Proceedings of the National Academy of Sciences, Vol. 93, Issue 23 https://doi.org/10.1073/pnas.93.23.12817	journal	November 1996
Kemp elimination catalysts by computational enzyme design Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M. Nature, Vol. 453, Issue 7192, p. 190-195 https://doi.org/10.1038/nature06879	journal	March 2008
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
Next-generation synthetic gene networks Lu, Timothy K.; Khalil, Ahmad S.; Collins, James J. Nature Biotechnology, Vol. 27, Issue 12 https://doi.org/10.1038/nbt.1591	journal	December 2009
Genetic Studies of the lac Repressor. XIV. Analysis of 4000 Altered Escherichia coli lac Repressors Reveals Essential and Non-essential Residues, as well as "Spacers" which do not Require a Specific Sequence Markiewicz, P.; Kleina, L. G.; Cruz, C. Journal of Molecular Biology, Vol. 240, Issue 5 https://doi.org/10.1006/jmbi.1994.1458	journal	July 1994
Prediction of functional specificity determinants from protein sequences using log-likelihood ratios Pei, J.; Cai, W.; Kinch, L. N. Bioinformatics, Vol. 22, Issue 2 https://doi.org/10.1093/bioinformatics/bti766	journal	November 2005
Arac/XylS family of transcriptional regulators. Gallegos, M. T.; Schleif, R.; Bairoch, A. Microbiology and molecular biology reviews : MMBR, Vol. 61, Issue 4 https://doi.org/10.1128/.61.4.393-410.1997	journal	January 1997
Recombineering with tolC as a Selectable/Counter-selectable Marker: remodeling the rRNA Operons of Escherichia coli DeVito, Joseph A. Nucleic Acids Research, Vol. 36, Issue 1 https://doi.org/10.1093/nar/gkm1084	journal	December 2007
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs Altschul, Stephen F.; Madden, Thomas L.; Schäffer, Alejandro A. Nucleic Acids Research, Vol. 25, Issue 17, p. 3389-3402 https://doi.org/10.1093/nar/25.17.3389	journal	September 1997
Transcription Factor-Based Screens and Synthetic Selections for Microbial Small-Molecule Biosynthesis Dietrich, Jeffrey A.; Shis, David L.; Alikhani, Azadeh ACS Synthetic Biology, Vol. 2, Issue 1 https://doi.org/10.1021/sb300091d	journal	September 2012
Evolution-guided optimization of biosynthetic pathways Raman, Srivatsan; Rogers, Jameson K.; Taylor, Noah D. Proceedings of the National Academy of Sciences, Vol. 111, Issue 50, p. 17803-17808 https://doi.org/10.1073/pnas.1409523111	journal	December 2014
Rosetta comparative modeling for library design: Engineering alternative inducer specificity in a transcription factor: A Comparative Approach for Protein Design Jha, Ramesh K.; Chakraborti, Subhendu; Kern, Theresa L. Proteins: Structure, Function, and Bioinformatics, Vol. 83, Issue 7 https://doi.org/10.1002/prot.24828	journal	May 2015
FLASH: fast length adjustment of short reads to improve genome assemblies Magoc, T.; Salzberg, S. L. Bioinformatics, Vol. 27, Issue 21 https://doi.org/10.1093/bioinformatics/btr507	journal	September 2011
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Flexibility in the Inducer Binding Region Is Crucial for Allostery in the Escherichia coli Lactose Repressor Xu, Jia; Matthews, Kathleen S. Biochemistry, Vol. 48, Issue 22 https://doi.org/10.1021/bi9002343	journal	June 2009
Using Orthologous and Paralogous Proteins to Identify Specificity-determining Residues in Bacterial Transcription Factors Mirny, Leonid A.; Gelfand, Mikhail S. Journal of Molecular Biology, Vol. 321, Issue 1 https://doi.org/10.1016/S0022-2836(02)00587-9	journal	August 2002
Evolutionarily conserved networks of residues mediate allosteric communication in proteins Süel, Gürol M.; Lockless, Steve W.; Wall, Mark A. Nature Structural Biology, Vol. 10, Issue 1 https://doi.org/10.1038/nsb881	journal	December 2002
Charting a course through RNA polymerase Bell, Stephen D.; Jackson, Stephen P. Nature Structural Biology, Vol. 7, Issue 9, p. 703-705 https://doi.org/10.1038/78907	journal	September 2000
Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis Strong, M.; Sawaya, M. R.; Wang, S. Proceedings of the National Academy of Sciences, Vol. 103, Issue 21 https://doi.org/10.1073/pnas.0602606103	journal	May 2006
Engineering and characterization of a superfolder green fluorescent protein Pédelacq, Jean-Denis; Cabantous, Stéphanie; Tran, Timothy Nature Biotechnology, Vol. 24, Issue 1, p. 79-88 https://doi.org/10.1038/nbt1172	journal	December 2005
Design and Application of a Mevalonate-Responsive Regulatory Protein Tang, Shuang-Yan; Cirino, Patrick C. Angewandte Chemie International Edition, Vol. 50, Issue 5 https://doi.org/10.1002/anie.201006083	journal	December 2010
Generation of Novel Bacterial Regulatory Proteins That Detect Priority Pollutant Phenols Wise, A. A.; Kuske, C. R. Applied and Environmental Microbiology, Vol. 66, Issue 1 https://doi.org/10.1128/AEM.66.1.163-169.2000	journal	January 2000
Engineering Transcriptional Regulator Effector Specificity Using Computational Design and In Vitro Rapid Prototyping: Developing a Vanillin Sensor de los Santos, Emmanuel L. C.; Meyerowitz, Joseph T.; Mayo, Stephen L. ACS Synthetic Biology, Vol. 5, Issue 4 https://doi.org/10.1021/acssynbio.5b00090	journal	August 2015
Plasticity of quaternary structure: Twenty-two ways to form a LacI dimer Swint-Kruse, L. Protein Science, Vol. 10, Issue 2 https://doi.org/10.1110/ps.35801	journal	February 2001
Effector Specificity Mutants of the Transcriptional Activator NahR of Naphthalene Degrading Pseudomonas Define Protein Sites Involved in Binding of Aromatic Inducers Cebolla, Angel; Sousa, Carolina; de Lorenzo, Víctor Journal of Biological Chemistry, Vol. 272, Issue 7 https://doi.org/10.1074/jbc.272.7.3986	journal	February 1997
AraC Regulatory Protein Mutants with Altered Effector Specificity Tang, Shuang-Yan; Fazelinia, Hossein; Cirino, Patrick C. Journal of the American Chemical Society, Vol. 130, Issue 15 https://doi.org/10.1021/ja7109053	journal	April 2008
De Novo Computational Design of Retro-Aldol Enzymes Jiang, L.; Althoff, E. A.; Clemente, F. R. Science, Vol. 319, Issue 5868 https://doi.org/10.1126/science.1152692	journal	March 2008
Molecular basis for control of antibiotic production by a bacterial hormone Zhou, Shanshan; Bhukya, Hussain; Malet, Nicolas Nature, Vol. 590, Issue 7846 https://doi.org/10.1038/s41586-021-03195-x	journal	February 2021
Design and Application of a Mevalonate-Responsive Regulatory Protein Tang, Shuang-Yan; Cirino, Patrick C. Angewandte Chemie, Vol. 123, Issue 5 https://doi.org/10.1002/ange.201006083	journal	December 2010
Directed evolution of Vibrio fischeri LuxR for increased sensitivity to a broad spectrum of acyl-homoserine lactones: Directed evolution of LuxR Collins, Cynthia H.; Arnold, Frances H.; Leadbetter, Jared R. Molecular Microbiology, Vol. 55, Issue 3 https://doi.org/10.1111/j.1365-2958.2004.04437.x	journal	December 2004
High-Throughput Metabolic Engineering: Advances in Small-Molecule Screening and Selection Dietrich, Jeffrey A.; McKee, Adrienne E.; Keasling, Jay D. Annual Review of Biochemistry, Vol. 79, Issue 1 https://doi.org/10.1146/annurev-biochem-062608-095938	journal	June 2010
Controlling Gene Expression in Living Cells Through Small Molecule-RNA Interactions Werstuck, G. Science, Vol. 282, Issue 5387 https://doi.org/10.1126/science.282.5387.296	journal	October 1998
Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements Lutz, R. Nucleic Acids Research, Vol. 25, Issue 6, p. 1203-1210 https://doi.org/10.1093/nar/25.6.1203	journal	March 1997
Screening and Identification of a Fungal β-Glucosidase and the Enzymatic Synthesis of Gentiooligosaccharide Qin, Yongling; Zhang, Yunkai; He, Haiyan Applied Biochemistry and Biotechnology, Vol. 163, Issue 8 https://doi.org/10.1007/s12010-010-9105-y	journal	October 2010
BLAT---The BLAST-Like Alignment Tool Kent, W. J. Genome Research, Vol. 12, Issue 4 https://doi.org/10.1101/gr.229202	journal	March 2002
Clustal W and Clustal X version 2.0 Larkin, M. A.; Blackshields, G.; Brown, N. P. Bioinformatics, Vol. 23, Issue 21, p. 2947-2948 https://doi.org/10.1093/bioinformatics/btm404	journal	September 2007
Programming cells by multiplex genome engineering and accelerated evolution Wang, Harris H.; Isaacs, Farren J.; Carr, Peter A. Nature, Vol. 460, Issue 7257, p. 894-898 https://doi.org/10.1038/nature08187	journal	July 2009
Directed evolution of protein switches and their application to the creation of ligand-binding proteins Guntas, G.; Mansell, T. J.; Kim, J. R. Proceedings of the National Academy of Sciences, Vol. 102, Issue 32 https://doi.org/10.1073/pnas.0502673102	journal	August 2005
Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Gossen, M.; Bujard, H. Proceedings of the National Academy of Sciences, Vol. 89, Issue 12 https://doi.org/10.1073/pnas.89.12.5547	journal	June 1992
Computational design of ligand-binding proteins with high affinity and selectivity Tinberg, Christine E.; Khare, Sagar D.; Dou, Jiayi Nature, Vol. 501, Issue 7466, p. 212-216 https://doi.org/10.1038/nature12443	journal	September 2013
Synthetic biosensors for precise gene control and real-time monitoring of metabolites Rogers, Jameson K.; Guzman, Christopher D.; Taylor, Noah D. Nucleic Acids Research, Vol. 43, Issue 15 https://doi.org/10.1093/nar/gkv616	journal	July 2015
A comparison of normalization methods for high density oligonucleotide array data based on variance and bias Bolstad, B. M.; Irizarry, R. A.; Astrand, M. Bioinformatics, Vol. 19, Issue 2 https://doi.org/10.1093/bioinformatics/19.2.185	journal	January 2003
Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips Kosuri, Sriram; Eroshenko, Nikolai; LeProust, Emily M. Nature Biotechnology, Vol. 28, Issue 12, p. 1295-1299 https://doi.org/10.1038/nbt.1716	journal	November 2010
A Directed Approach for Engineering Conditional Protein Stability Using Biologically Silent Small Molecules Maynard-Smith, Lystranne A.; Chen, Ling-chun; Banaszynski, Laura A. Journal of Biological Chemistry, Vol. 282, Issue 34 https://doi.org/10.1074/jbc.M703902200	journal	July 2007
Perturbation from a Distance: Mutations that Alter LacI Function through Long-Range Effects ^† Swint-Kruse, Liskin; Zhan, Hongli; Fairbanks, Bonnie M. Biochemistry, Vol. 42, Issue 47 https://doi.org/10.1021/bi035116x	journal	December 2003
Comparison of 15 dinoflagellate genomes reveals extensive sequence and structural divergence in family Symbiodiniaceae and genus Symbiodinium González-Pech, Raúl A.; Stephens, Timothy G.; Chen, Yibi BMC Biology, Vol. 19, Issue 1 https://doi.org/10.1186/s12915-021-00994-6	journal	April 2021
Genetic Studies of the Lac Repressor XV: 4000 Single Amino Acid Substitutions and Analysis of the Resulting Phenotypes on the Basis of the Protein Structure Suckow, Jörg; Markiewicz, Peter; Kleina, Lynn G. Journal of Molecular Biology, Vol. 261, Issue 4 https://doi.org/10.1006/jmbi.1996.0479	journal	August 1996
Conformer Generation with OMEGA: Learning from the Data Set and the Analysis of Failures Hawkins, Paul C. D.; Nicholls, Anthony Journal of Chemical Information and Modeling, Vol. 52, Issue 11 https://doi.org/10.1021/ci300314k	journal	November 2012
Novel insights from hybrid LacI/GalR proteins: family-wide functional attributes and biologically significant variation in transcription repression Meinhardt, Sarah; Manley, Michael W.; Becker, Nicole A. Nucleic Acids Research, Vol. 40, Issue 21 https://doi.org/10.1093/nar/gks806	journal	September 2012
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Emergence of novel functions in transcriptional regulators by regression to stem protein types Galvão, Teca Calcagno; Mencía, Mario; de Lorenzo, Víctor Molecular Microbiology, Vol. 65, Issue 4 https://doi.org/10.1111/j.1365-2958.2007.05832.x	journal	August 2007
Molecular Biology of the LysR Family of Transcriptional Regulators Schell, M. A. Annual Review of Microbiology, Vol. 47, Issue 1 https://doi.org/10.1146/annurev.mi.47.100193.003121	journal	October 1993
Use of TLS parameters to model anisotropic displacements in macromolecular refinement Winn, M. D.; Isupov, M. N.; Murshudov, G. N. Acta Crystallographica Section D Biological Crystallography, Vol. 57, Issue 1 https://doi.org/10.1107/S0907444900014736	journal	January 2001
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products Datsenko, K. A.; Wanner, B. L. Proceedings of the National Academy of Sciences, Vol. 97, Issue 12, p. 6640-6645 https://doi.org/10.1073/pnas.120163297	journal	May 2000
Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database Hawkins, Paul C. D.; Skillman, A. Geoffrey; Warren, Gregory L. Journal of Chemical Information and Modeling, Vol. 50, Issue 4 https://doi.org/10.1021/ci100031x	journal	March 2010
Complete Genome Sequence of Clostridium botulinum CJ0611A1, a Type A(B) Isolate Associated with an International Outbreak of Botulism from Commercial Carrot Juice Harris, Richard; Dussault, Forest; Flint, Annika Microbiology Resource Announcements, Vol. 10, Issue 1 https://doi.org/10.1128/mra.01111-20	journal	January 2021
Engineering allostery Raman, Srivatsan; Taylor, Noah; Genuth, Naomi Trends in Genetics, Vol. 30, Issue 12 https://doi.org/10.1016/j.tig.2014.09.004	journal	December 2014
Genome Scale Reconstruction of a Salmonella Metabolic Model: COMPARISON OF SIMILARITY AND DIFFERENCES WITH A COMMENSAL Escherichia coli STRAIN AbuOun, Manal; Suthers, Patrick F.; Jones, Gareth I. Journal of Biological Chemistry, Vol. 284, Issue 43 https://doi.org/10.1074/jbc.M109.005868	journal	August 2009
A family of bacterial regulators homologous to Gal and Lac repressors. Weickert, M. J.; Adhya, S. Journal of Biological Chemistry, Vol. 267, Issue 22 https://doi.org/10.1016/S0021-9258(19)49615-4	journal	August 1992
Purification and properties of Gal repressor:pL-galR fusion in pKC31 plasmid vector. Majumdar, A.; Rudikoff, S.; Adhya, S. Journal of Biological Chemistry, Vol. 262, Issue 5 https://doi.org/10.1016/S0021-9258(18)61657-6	journal	February 1987

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Numerical operations in living cells by programmable RNA devices Endo, Kei; Hayashi, Karin; Saito, Hirohide Science Advances, Vol. 5, Issue 8 https://doi.org/10.1126/sciadv.aax0835	journal	August 2019
Overcoming genetic heterogeneity in industrial fermentations Rugbjerg, Peter; Sommer, Morten O. A. Nature Biotechnology, Vol. 37, Issue 8 https://doi.org/10.1038/s41587-019-0171-6	journal	July 2019
Commentary: Synthetic Addiction Extends the Productive Life Time of Engineered Escherichia coli Populations Enrico Bena, Chiara; Grob, Alice; Isalan, Mark Frontiers in Bioengineering and Biotechnology, Vol. 6 https://doi.org/10.3389/fbioe.2018.00077	journal	June 2018
Structural and functional analyses of the cellulase transcription regulator CelR Fu, Yaoyao; Yeom, Soo‐Jin; Kwon, Kil Koang FEBS Letters, Vol. 592, Issue 16 https://doi.org/10.1002/1873-3468.13206	journal	August 2018
Dynamic metabolic control: towards precision engineering of metabolism Liu, Di; Mannan, Ahmad A.; Han, Yichao Journal of Industrial Microbiology & Biotechnology, Vol. 45, Issue 7 https://doi.org/10.1007/s10295-018-2013-9	journal	January 2018
A paper-based, cell-free biosensor system for the detection of heavy metals and date rape drugs Gräwe, Alexander; Dreyer, Anna; Vornholt, Tobias PLOS ONE, Vol. 14, Issue 3 https://doi.org/10.1371/journal.pone.0210940	journal	March 2019
Tools and systems for evolutionary engineering of biomolecules and microorganisms Jang, Sungho; Kim, Minsun; Hwang, Jaeseong Journal of Industrial Microbiology & Biotechnology, Vol. 46, Issue 9-10 https://doi.org/10.1007/s10295-019-02191-5	journal	May 2019
Archimedes’ principle for characterisation of recombinant whole cell biocatalysts Schmitt, Steven; Walser, Marcel; Rehmann, Michael Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-20877-1	journal	February 2018
A self-inducible heterologous protein expression system in Escherichia coli Briand, L.; Marcion, G.; Kriznik, A. Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep33037	journal	September 2016
Unified rational protein engineering with sequence-based deep representation learning Alley, Ethan C.; Khimulya, Grigory; Biswas, Surojit Nature Methods, Vol. 16, Issue 12 https://doi.org/10.1038/s41592-019-0598-1	journal	October 2019
Sort-Seq Approach to Engineering a Formaldehyde-Inducible Promoter for Dynamically Regulated Escherichia coli Growth on Methanol Rohlhill, Julia; Sandoval, Nicholas R.; Papoutsakis, Eleftherios T. ACS Synthetic Biology, Vol. 6, Issue 8, p. 1584-1595 https://doi.org/10.1021/acssynbio.7b00114	journal	May 2017
The Role of Protein Engineering in Biomedical Applications of Mammalian Synthetic Biology Bojar, Daniel; Fussenegger, Martin Small, Vol. 16, Issue 27 https://doi.org/10.1002/smll.201903093	journal	October 2019

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