Selected Publications

2013

• Dellus-Gur E, Toth-Petroczy A, Elias M, Tawfik DS. “What Makes a Protein Fold Amenable to Functional Innovation? Fold Polarity and Stability Trade-offs.” J Mol Biol 2013 Mar 28.

• Bar-Even A, Tawfik DS. “Engineering specialized methabolic pathways - is there a room for enzyme improvements?” Curr Op in Biot 24:310-319

• Goldsmith M, Tawfik DS. “Enzyme Engineering by Targeted Libraries.” Methods in Enzymology Vol. 523

• Ben-David M, Wieczorek G, Elias M, Silman I, Sussman JL, Tawfik DS. “Catalytic Metal Ion Rearrangements Underline Promiscuity and Evolvability of a Metalloenzyme.” J Mol Biol. 2013 Jan

• Tóth-Petróczy A, Tawfik DS. “Protein Insertions and Deletions Enabled by Neutral Roaming in Sequence Space.” Mol Biol Evol. 2013 Jan

  2012

• Tokuriki N, Jackson CJ, Afriat-Jurnou L, Wyganowski KT, Tang R, Tawfik DS. “Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme.” Nat Commun.2012;3:1257.

• Rockah-Shmuel L, Tawfik DS. “Evolutionary transitions to new DNA methyltransferases through target site expansion and shrinkage.” Nucleic Acids Res. 2012 Oct 15.

• Elias M, Wellner A, Goldin-Azulay K, Chabriere E, Vorholt JA, Erb TJ, Tawfik DS. “The molecular basis of phosphate discrimination in arsenate-rich environments.” Nature 2012 Oct 3. Nature News: ‘Arsenic-life’ bacterium prefers phosphorus after all.

• Afriat-Jurnou L, Jackson CJ, Tawfik DS. “Reconstructing a Missing Link in the Evolution of a Recently Diverged Phosphotriesterase by Active-Site Loop Remodeling.” Biochemistry 2012 Jul 30.

• Khersonsky O, Kiss G, Röthlisberger D, Dym O, Albeck S, Houk KN, Baker D, Tawfik DS. “Bridging the gaps in design methodologies by evolutionary optimization of the stability and proficiency of designed Kemp eliminase KE59.” PNAS 2012 Jun 26;109(26):10358-63.

• Kipnis Y, Dellus-Gur E, Tawfik DS. “TRINS: a method for gene modification by randomized tandem repeat insertions.” Protein Eng Des Sel. 2012 Jun 4.

• Goldsmith M, Tawfik DS. “Directed enzyme evolution: beyond the low-hanging fruit.” Curr Opin Struct Biol. 2012 Aug;22(4):406-12.

• Goldsmith M, Ashani Y, Simo Y, Ben-David M, Leader H, Silman I, Sussman JL, Tawfik DS. “Evolved stereoselective hydrolases for broad-spectrum g-type nerve agent detoxification.” Chem Biol. 2012 Apr 20;19(4):456-66.

• Ben-David M, Elias M, Filippi JJ, Duñach E, Silman I, Sussman JL, Tawfik DS. “Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1.” J Mol Biol. 2012 May 4;418(3-4):181-96.

• Khare SD, Kipnis Y, Greisen P Jr, Takeuchi R, Ashani Y, Goldsmith M, Song Y, Gallaher JL, Silman I, Leader H, Sussman JL, Stoddard BL, Tawfik DS, Baker D. “Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis.” Nature Chem Biol. 2012 Feb 5;8(3):294-300.

• Elias M, Tawfik DS. “Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases.” J Biol Chem. 2012 Jan 2;287(1):11-20.

  2011

• Bar-Even, A., Noor, E., Savir, Y., Liebermeister, W., Davidi, D., Tawfik, D.S. & Milo, R. “The moderately efficient enzyme: evolutionary and physico-chemical trends shaping enzyme parameters.” Biochemistry (2011) 50: 4402-4410 .

• Ashani Y, Goldsmith M, Leader H, Silman I, Sussman JL, Tawfik DS. “In vitro detoxification of cyclosarin in human blood pre-incubated ex vivo with recombinant serum paraoxonases.” Toxicol Lett. (2011) Sep 25;206(1):24-8.

• Alcolombri U, Elias M, Tawfik DS. “Directed Evolution of Sulfotransferases and Paraoxonases by Ancestral Libraries.” JMB (2011) Aug 26;411(4):837-53.

• Tóth-Petróczy Á, Tawfik DS. “Slow protein evolutionary rates are dictated by surface-core association.” PNAS (2011) June; 108 (27) 11151-11156.

• Salverda ML, Dellus E, Gorter FA, Debets AJ, van der Oost J, Hoekstra RF, Tawfik DS, de Visser JA. “Initial mutations direct alternative pathways of protein evolution.” PLoS Genet (2011) Mar;7(3):e1001321.

• Khersonsky O, Malitsky S, Rogachev I, Tawfik DS. “Role of chemistry versus substrate binding in recruiting promiscuous enzyme functions.” Biochemistry (2011) Apr 5;50(13):2683-90.

• Khersonsky O, Röthlisberger D, Wollacott AM, Murphy P, Dym O, Albeck S, Kiss G, Houk KN, Baker D, Tawfik DS. “Optimization of the in-silico-designed kemp eliminase KE70 by computational design and directed evolution.” JMB (2011) Apr 1;407(3):391-412.

• Tawfik DS, Viola RE. “Arsenate replacing phosphate - alternative life chemistries and ion promiscuity.” Biochemistry (2011) Jan;7.

• Gupta RD, Goldsmith M, Ashani Y, Simo Y, Mullokandov G, Bar H, Ben-David M, Leader H, Margalit R, Silman I, Sussman JL, Tawfik DS. “Directed evolution of hydrolases for prevention of G-type nerve agent intoxication.” NatChemBio (2011) Feb;7(2):120-5.

• Yadid I, Tawfik DS. “Functional beta-propeller lectins by tandem duplications of repetitive units.” PEDS (2011) Jan;24(1-2):185-95.

  2010

• Tawfik DS. “Messy biology and the origins of evolutionary innovations.” NatChemBio (2010) Oct;6(10):692-6.

• Soskine M, Tawfik DS. “Mutational effects and the evolution of new protein functions.” Nat Rev Genet. (2010) Aug;11(8):572-582.

• Olga Khersonsky and Dan S. Tawfik. „In Comprehensive Natural Products II Chemistry and Biology”; Mander, L., Lui, H.-W., Eds.; Elsevier: Oxford (2010); volume 8, pp.48–90.

• Yadid I, Kirshenbaum N, Sharon M, Dym O, Tawfik DS. “Metamorphic proteins mediate evolutionary transitions of structure.” Proc Natl Acad Sci U S A (2010) Apr 20;107(16):7287-7292.

• Ashani Y, Gupta RD, Goldsmith M, Silman I, Sussman JL, Tawfik DS, Leader H. “Stereo-specific synthesis of analogs of nerve agents and their utilization for selection and characterization of paraoxonase (PON1) catalytic scavengers.” Chem Biol Interact. (2010) Mar 19.

• Khersonsky O, Tawfik DS. “Enzyme promiscuity: a mechanistic and evolutionary perspective.” Annu Rev Biochem. (2010);79:471-505.

• Khersonsky O, Röthlisberger D, Dym O, Albeck S, Jackson CJ, Baker D, Tawfik DS. “Evolutionary optimization of computationally designed enzymes: Kemp eliminases of the KE07 series.” J Mol Biol. (2010) Mar 5;396(4):1025-1042.

• Gaidukov L, Viji RI, Yacobson S, Rosenblat M, Aviram M, Tawfik DS. “ApoE induces serum paraoxonase PON1 activity and stability similar to ApoA-I.” Biochemistry (2010) Jan 26;49(3):532-538.

  2009

• Khersonsky O, Rosenblat M, Toker L, Yacobson S, Hugenmatter A, Silman I, Sussman JL, Aviram M, Tawfik DS. "Directed evolution of serum paraoxonase PON3 by family shuffling and ancestor/consensus mutagenesis, and its biochemical characterization." Biochemistry (2009) Jul 21;48(28):6644-54.

• Jackson CJ, Foo JL, Tokuriki N, Afriat L, Carr PD, Kim HK, Schenk G, Tawfik DS, Ollis DL. “Conformational sampling, catalysis, and evolution of the bacterial phosphotriesterase.” Proc Natl Acad Sci U S A (2009) Dec 22;106(51):21631-21636.

• Gaidukov L, Bar D, Yacobson S, Naftali E, Kaufman O, Tabakman R, Tawfik DS, Levy-Nissenbaum E. “In vivo administration of BL-3050: highly stable engineered PON1-HDL complexes.” BMC Clin Pharmacol. (2009) Nov 17;9:18.

• Tokuriki N, Tawfik DS. “Stability effects of mutations and protein evolvability.” Curr Opin Struct Biol. (2009) Oct;19(5):596-604.

• Barnath-Levin K, Dym O, Albeck S, Magdassi S, Keeble AH, Kleanthous C, Tawfik DS. “Following evolutionary paths to protein-protein interactions with high affinity and selectivity.” Nat Struct Mol Biol. (2009) Oct;16(10):1049-1055.

• Tokuriki N, Tawfik DS. “Chaperonin overexpression promotes genetic variation and enzyme evolution.” Nature (2009) June 4;459(7247):668-673.

• Tokuriki N, Tawfik DS. “Protein dynamism and evolvability.” Science (2009) Apr 10;324(5924):203-207.

• Goldsmith M, Tawfik DS. “Potential role of phenotypic mutations in the evolution of protein expression and stability.” Proc Natl Acad Sci U S A., (2009) Apr 14;106(15):6197-6202.

• Tokuriki N, Oldfield CJ, Uversky VN, Berezovsky IN, Tawfik DS. ”Do viral proteins possess unique biophysical features?” Trends Biochem Sci. (2009) Feb;34(2):53-59.

  2008

• Gupta RD, Tawfik DS. “Directed enzyme evolution via small and effective neutral drift libraries.” Nat Methods. (2008) Nov;5(11):939-942.

• Bershtein S, Tawfik DS. “Ohno's model revisited: measuring the frequency of potentially adaptive mutations under various mutational drifts.” Mol Biol Evol. (2008) Nov;25(11):2311-2318.

• Shimon Bershtein, Korina Goldin, Tawfik DS. "Intense Neutral Drifts Yield Robust and Evolvable Consensus Proteins." J Mol Biol. (2008) June;379(5):1029–1044.

• Röthlisberger D, Khersonsky O, Wollacott AM, Jiang L, DeChancie J, Betker J, Gallaher JL, Althoff EA, Zanghellini A, Dym O, Albeck S, Houk KN, Tawfik DS, Baker D. "Kemp elimination catalysts by computational enzyme design." Nature (2008) May 8;453(7192):190-195.

• Bershtein S, Tawfik DS. "Advances in laboratory evolution of enzymes." Curr Opin Chem Biol. (2008) Apr;12(2):151-158.

• Tokuriki N, Stricher F, Serrano L, Tawfik DS. "How protein stability and new functions trade off." PLoS Comput Biol. (2008) Feb 29;4(2):2-7.

  2007

• Goldsmith M, Kiss C, Bradbury AR, Tawfik DS. "Avoiding and controlling double transformation artifacts." Protein Eng Des Sel. (2007) Jul;20(7):315-318.

• Peisajovich SG, Tawfik DS. "Protein engineers turned evolutionists." Nat. Methods (2007) Dec;4(12):991-994.

• Amitai G, Devi Gupta R, Tawfik DS. "Latent evolutionary potentials under the neutral mutational drift of an enzyme." HFSP Journal, May (2007);1(1):67-78.

• Tokuriki N, Stricher F, Schymkowitz J, Serrano L, Tawfik DS. "The stability effects of protein mutations appear to be universally distributed." J. Mol. Biol. (2007) Jun 22;369(5):1318-1332.

• Gaidukov L, Tawfik DS. "The development of human sera tests for HDL-bound serum PON1 and its lipolactonase activity." J. Lipid Res. (2007) Jul;48(7):1637-1646.

• Herman A, Tawfik DS. "Incorporating Synthetic Oligonucleotides via Gene Reassembly (ISOR): a versatile tool for generating targeted libraries." Protein Eng. Des. Sel. (2007) May;20(5):219-226.

• Yadid I, Tawfik DS. "Reconstruction of functional β-propeller lectins via homo-oligomeric assembly of shorter fragments." J Mol Biol. (2007) Jan 5;365(1):10-17.

  2006

• Bershtein S, Segal M, Bekerman R, Tokuriki N, Tawfik DS. "Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein." Nature (2006) Dec 14;444(7121):929-932.

• Afriat L, Roodveldt C, Manco G, Tawfik DS. "The latent promiscuity of newly identified microbial lactonases is linked to a recently diverged phosphotriesterase." Biochemistry (2006) Nov 21;45(46):13677-13686.

• Khersonsky O, Roodveldt C, Tawfik DS. "Enzyme promiscuity: evolutionary and mechanistic aspects." Curr Opin Chem Biol. (2006) Oct;10(5):498-508.

• Griffiths AD, Tawfik DS. "Miniaturising the laboratory in emulsion droplets." Trends Biotechnol. (2006) Jul 13;30(10):1-8..

• Miller OJ, Bernath K, Agresti JJ, Amitai G, Kelly BT, Mastrobattista E, Taly V, Magdassi S, Tawfik DS, Griffiths AD. "Directed evolution by in vitro compartmentalization." Nat Methods. (2006) Jul;3(7):561-570.

• Williams R, Peisajovich SG, Miller OJ, Magdassi S, Tawfik DS, Griffiths AD. "Amplification of complex gene libraries by emulsion PCR." Nat Methods (2006) Jul;3(7):545-550.

• Amitai G, Gaidukov L, Adani R, Yishay S, Yacov G, Kushnir M, Teitlboim S, Lindenbaum M, Bel P, Khersonsky O, Tawfik DS, Meshulam H. (2006) "Enhanced stereoselective hydrolysis of toxic organophosphates by directly evolved variants of mammalian serum paraoxonase." FEBS J., (2006) May;273(9):1906-1919.

• Tawfik DS. "Loop grafting and the origins of enzyme species." Science. (2006) Jan 27;311(5760):475-476.

• Peisajovich SG, Rockah L, Tawfik DS. "Evolution of new protein topologies through multistep gene rearrangements." Nat Genet. (2006) Feb;38(2):168-174.

• Khersonsky O, Tawfik DS. "The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases." J Biol Chem. (2006) Mar 17;281(11):7649-7656.

• Rosenblat M, Gaidukov L, Khersonsky O, Vaya J, Oren R, Tawfik DS, Aviram M. (2006) "The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux." J Biol Chem. (2006) Mar 17;281(11):7657-7665.

  2005

• Aharoni A, Amitai G, Bernath K, Magdassi S, Tawfik DS. "High-throughput screening of enzyme libraries: thiolactonases evolved by fluorescence-activated sorting of single cells in emulsion compartments." (2005) Chem Biol., (2005) Dec;12(12):1281-1289.

• Khersonsky O, Tawfik DS. "Chromogenic and fluorogenic assays for the lactonase activity of serum paraoxonases." (2006) Chembiochem., (2006) Jan;7(1):49-53.

• Roodveldt C, Tawfik DS. "Shared promiscuous activities and evolutionary features in various members of the amidohydrolase superfamily." (2005) Biochemistry, (2005) Sep 27;44(38):12728-12736.

• James LC, Tawfik DS. "Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition." (2005) Proc Natl Acad Sci U S A., (2005) Sep 6;102(36):12730-12735.

• Gaidukov L, Tawfik DS. "High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I." (2005) Biochemistry, (2005) Sep 6;44(35):11843-11854.

• Roodveldt C, Aharoni A, Tawfik DS. (2005) "Directed evolution of proteins for heterologous expression and stability." Curr Opin Struct Biol., 2005 Feb;15(1):50-56.

• Roodveldt C, Tawfik DS. (2005) "Directed evolution of phosphotriesterase from Pseudomonas diminuta for heterologous expression in Escherichia coli results in stabilization of the metal-free state." Protein Eng Des Sel., 2005 Jan;18(1):51-58.

• Khersonsky O, Tawfik DS. (2005) "Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase." Biochemistry, 2005 Apr 26;44(16):6371-6382.

• Aharoni A, Griffiths AD, Tawfik DS. (2005) "High-throughput screens and selections of enzyme-encoding genes." Curr Opin Chem Biol., 2005 Apr 9;(2):210-216.

• Gould SM, Tawfik DS. "Directed evolution of the promiscuous esterase activity of carbonic anhydrase II." Biochemistry, (2005) Apr 12;44(14):5444-5452.

• Bernath, K., Magdassi, S. & Tawfik, D.S. "Directed evolution of immunity protein inhibitors of colicin DNA-nucleases by in vitro compartmentalization (IVC) and nanodroplet delivery." J. Mol. Biol. (2005) Feb 4;345(5):1015-1026..

• Aharoni, A., Gaidukov, L., Khersonsky, O., Gould, McQ. S., Roodveldt, C. & Tawfik, D.S. "The evolvability of promiscuous protein functions." Nature Genetics (2005) 37:73-76.

  2004

• Harel, M., Aharoni, A., Gaidukov, L., Brumshtein, B., Khersonsky, O., Meged, R., Dvir, H., Ravelli, R.B.G., McCarthy, A., Toker, L., Silman, I., Sussman, J.L. & Tawfik, D.S. "Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotc enzymes." Nature Struct. & Mol. Biol. (2004) 11:412-419.

• Aharoni, A. & Tawfik, D.S. "Directed evolution of recombinant serum paraoxonase (PON) variants." Discovery Medicine (2004) 4:120-124.

• Bernath, K., Hai, M., Mastrobattista, E., Griffiths,A.D., Magdassi, S. & Tawfik, D.S. "In vitro compartmentalization by double emulsions: Sorting and gene enrichment by fluorescent activated cell sorting (FACS)." Anal. Biochem. (2004) 325:151-157.

• Bernath, K., Magdassi, S, & Tawfik, D.S. "In vitro compartmentalization (IVC): A high-throughput screening technology using emulsions and FACS. Discovery Medicine (2004) 4: 49-53.

• Cohen, H.M., Tawfik, D.S. & Griffiths, A.D. "Altering the sequence specificity of HaeIII methyltransferase by directed evolution using in vitro compartmentalization." PEDS (2004) 17:3-11.

• Aharoni, A., Gaidukov, L., Yagur, S., Toker, L., Silman, I. & Tawfik, D.S. "Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial expression and catalytic specialization." Proc. Natl. Acad. Sci. USA. (2004) 101: 482-487.

  2003

• James, L.C & Tawfik, D.S. "The specificity of cross-reactivity: Promiscuous antibody binding involves specific hydrogen-bonds rather than non-specific hydrophobic stickiness." Protein Sci. (2003) 12:2183-2193.

• James, L.C & Tawfik, D.S. "Conformational diversity and protein evolution – a 60 year old hypothesis revisited." Trends Biochem. Sci. (TiBS) (2003) 28:361-368.

• James, L.C., Roversi, P. & Tawfik, D.S. "Antibody multi-specificity mediated by conformational diversity." Science (2003) 299:1362-1367.

• Griffiths, A.D. & Tawfik, D.S. "Directed evolution of an extremely fast phosphotriesterase by in vitro compartmentalisation." EMBO J. (2003) 22:24-35.

  2002

• Sepp, A., Tawfik, D.S. & Griffiths, A.D. "Microbead display by in vitro compartmentalisation: Selection for binding using flow cytometry." FEBS Lett (2002) 532:455-458.

• Lee, Y-F., Tawfik, D.S. & Griffiths, A.D. "Investigating the target recognition of DNA cytosine-5-methyltransferase HhaI by library selection using in vitro compartmentalisation (IVC)." Nucleic Acid Res. (2002) 30:4937-4944.

• Cohen, H.M., Tawfik, D.S. & Griffiths, A.D. "Promiscuous methylation of many non-canonical sites by HaeIII methyltransferase." Nucleic Acid Res. (2002) 30:3880-3885.

• Lindner, A.B., Kim, S.-H., Schindler, D., Eshhar, Z. & Tawfik, D.S. "Esterolytic antibodies as mechanistic and structural models of hydrolases – a quantitative analysis." J. Mol. Biol. (2002) 320:559-572.

  Until 2001

• James, L.C. & Tawfik, D.S. "Catalytic and binding poly-reactivities shared by two unrelated proteins - the potential role of promiscuity in enzyme evolution." Protein Sci. (2001) 10: 2600-2607.

• Hollfelder, F., Kirby, A.J. & Tawfik, D.S. "On the magnitude and specificity of medium effects in enzyme-like catalysts." J. Org. Chem. (2001) 66:5866-5874.

• Griffiths, A.D. & Tawfik, D.S. "Man-made enzymes – from design to in vitro compartmentalisation." Curr Opin Biotech. (2000) 11:338-353.

• Lindner, A.B., Eshhar, Z. & Tawfik, D.S. "Conformational changes affect binding and catalysis by ester hydrolysing antibodies." J. Mol. Biol. (1999) 285:421-430.

• Tawfik, D.S. & Griffiths, A.D. "Man-made cell-like compartments for molecular evolution." Nature Biotechnology (1998) 16:652-656.

• Hollfelder, F., Kirby, A.J. & Tawfik, D.S. "Off-the-shelf proteins that rival tailor-made antibodies as catalysts." Nature (1996) 383:60-63.