Enzyme promiscuity: evolutionary and mechanistic aspects
Abstract
The past few years have seen significant advances in research related to the 'latent skills' of enzymes - namely, their capacity to promiscuously catalyze reactions other than the ones they evolved for. These advances regard (i) the mechanism of catalytic promiscuity - how enzymes, that generally exert exquisite specificity, promiscuously catalyze other, and sometimes barely related, reactions; (ii) the evolvability of promiscuous functions - namely, how latent activities evolve further, and in particular, how promiscuous activities can firstly evolve without severely compromising the original activity. These findings have interesting implications on our understanding of how new enzymes evolve. They support the key role of catalytic promiscuity in the natural history of enzymes, and suggest that today's enzymes diverged from ancestral proteins catalyzing a whole range of activities at low levels, to create families and superfamilies of potent and highly specialized enzymes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cumulative number of cell divisions (CCD) was proposed as a more appropriate denominator to evaluate microbial evolution.
“Only recently, the cumulative number of cell divisions (CCD) was proposed as a more appropriate denominator to evaluate microbial evolution [126].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [126]
Cites
Ohno, S. (1970) · doi:10.1007/978-3-642-86659-3 · Cited by 7,833 · see citing works
Preservation of Duplicate Genes by Complementary, Degenerative Mutations
Force, A., Lynch, M., Pickett, F. B., Amores, A., Yan, Y.-L., & Postlethwait, J. (1999) · Genetics · doi:10.1093/genetics/151.4.1531 · Cited by 3,529 · see citing works
Jacob, F. (1977) · Science · doi:10.1126/science.860134 · Cited by 2,711 · see citing works
Structure and Mechanism in Protein Science
Fersht, A. (1998) · Cited by 1,890 · see citing works
The Probability of Duplicate Gene Preservation by Subfunctionalization
Lynch, M. F., & Force, A. G. (2000) · Genetics · doi:10.1093/genetics/154.1.459 · Cited by 1,557 · see citing works
Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins
Weinreich, D. M., Delaney, N. F., DePristo, M. A., & Hartl, D. L. (2006) · Science · doi:10.1126/science.1123539 · Cited by 1,418 · see citing works
Kirschner, M., & Gerhart, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8420 · Cited by 1,129 · see citing works
ENZYME RECRUITMENT IN EVOLUTION OF NEW FUNCTION
Jensen, R. A. (1976) · Annual Review of Microbiology · doi:10.1146/annurev.mi.30.100176.002205 · Cited by 1,108 · see citing works
Cytochromes P450 as versatile biocatalysts
Bernhardt, R. (2006) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2006.01.026 · Cited by 888 · see citing works
The 'evolvability' of promiscuous protein functions
Aharoni, A., Gaidukov, L., Khersonsky, O., Gould, S. M., Roodveldt, C., & Tawfik, D. S. (2004) · Nature Genetics · doi:10.1038/ng1482 · Cited by 833 · see citing works
Self-citationOptimality and evolutionary tuning of the expression level of a protein
Dekel, E., & Alon, U. (2005) · Nature · doi:10.1038/nature03842 · Cited by 766 · see citing works
Structural basis for ligand promiscuity in cytochrome P450 3A4
Ekroos, M., & Sjögren, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603236103 · Cited by 760 · see citing works
Catalytic promiscuity and the evolution of new enzymatic activities
O’Brien, P., & Herschlag, D. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80033-7 · Cited by 731 · see citing works
Draganov, D. I., Teiber, J. F., Speelman, A., Osawa, Y., Sunahara, R. K., & Du, B. N. L. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400511-jlr200 · Cited by 716 · see citing works
Resurrecting the Ancestral Steroid Receptor: Ancient Origin of Estrogen Signaling
Thornton, J. W., Need, E. F., & Crews, D. P. (2003) · Science · doi:10.1126/science.1086185 · Cited by 700 · see citing works
Robustness and evolvability: a paradox resolved
Wagner, A. (2008) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2007.1137 · Cited by 669 · see citing works
Perelson, A. S., & OSTER, G. F. (1979) · Journal of Theoretical Biology · doi:10.1016/0022-5193(79)90275-3 · Cited by 648 · see citing works
Enzyme promiscuity: mechanism and applications
Hult, K., & Berglund, P. (2007) · Trends in biotechnology · doi:10.1016/j.tibtech.2007.03.002 · Cited by 637 · see citing works
Catalytic Promiscuity in Biocatalysis: Using Old Enzymes to Form New Bonds and Follow New Pathways
Bornscheuer, U. T., & Kazlauskas, R. J. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200460416 · Cited by 604 · see citing works
Evolution of Hormone-Receptor Complexity by Molecular Exploitation
Bridgham, J. T., Carroll, S. M., & Thornton, J. W. (2006) · Science · doi:10.1126/science.1123348 · Cited by 601 · see citing works
Conformational diversity and protein evolution – a 60-year-old hypothesis revisited
James, L. C., & Tawfik, D. S. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00135-x · Cited by 579 · see citing works
Self-citationLipases as practical biocatalysts
Reetz, M. T. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00297-1 · Cited by 543 · see citing works
Gerlt, J. A., & Babbitt, P. C. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.209 · Cited by 540 · see citing works
Enzymes with extra talents: moonlighting functions and catalytic promiscuity
Copley, S. D. (2003) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(03)00032-2 · Cited by 522 · see citing works
The population genetics of ecological specialization in evolving Escherichia coli populations
Cooper, V. S., & Lenski, R. E. (2000) · Nature · doi:10.1038/35037572 · Cited by 519 · see citing works
Loss of Protein Structure Stability as a Major Causative Factor in Monogenic Disease
Yue, P., Li, Z. A., & Moult, J. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.08.020 · Cited by 518 · see citing works
On Some Principles Governing Molecular Evolution
Kimura, M., & Ohta, T. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.7.2848 · Cited by 503 · see citing works
Natural Selection and the Concept of a Protein Space
Smith, J. (1970) · Nature · doi:10.1038/225563a0 · Cited by 488 · see citing works
Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs
Wang, X., Minasov, G., & Shoichet, B. K. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00400-x · Cited by 462 · see citing works
Structure−Reactivity Studies of Serum Paraoxonase PON1 Suggest that Its Native Activity Is Lactonase
Khersonsky, O., & Tawfik, D. S. (2005) · Biochemistry · doi:10.1021/bi047440d · Cited by 459 · see citing works
Self-citationDesigned divergent evolution of enzyme function
Yoshikuni, Y., Ferrin, T. E., & Keasling, J. D. (2006) · Nature · doi:10.1038/nature04607 · Cited by 438 · see citing works
Energy Constraints on the Evolution of Gene Expression
Wagner, A. (2005) · Molecular Biology and Evolution · doi:10.1093/molbev/msi126 · Cited by 419 · see citing works
Sesquiterpene Synthases from Grand Fir (Abies grandis)
Steele, C. L., Crock, J. E., Bohlmann, J., & Croteau, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.2078 · Cited by 415 · see citing works
The Stability Effects of Protein Mutations Appear to be Universally Distributed
Tokuriki, N., Stricher, F., Schymkowitz, J. W. H., Serrano, L. G., & Tawfik, D. S. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.03.069 · Cited by 415 · see citing works
Self-citationRobustness–epistasis link shapes the fitness landscape of a randomly drifting protein
Bershtein, S., Segal, M., Bekerman, R., Tokuriki, N., & Tawfik, D. S. (2006) · Nature · doi:10.1038/nature05385 · Cited by 414 · see citing works
Self-citationOhno's dilemma: Evolution of new genes under continuous selection
Bergthorsson, U., Andersson, D. I., & Roth, J. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707158104 · Cited by 405 · see citing works
Newcomb, R. D., Campbell, P. M., Ollis, D. L., Cheah, E., Russell, R. J., & Oakeshott, J. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7464 · Cited by 378 · see citing works
Thermodynamic prediction of protein neutrality
Bloom, J. D., Silberg, J. J., Wilke, C. O., Drummond, D. A., Adami, C., & Arnold, F. H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406744102 · Cited by 354 · see citing works
Angiogenic activity of enzymes
Haraguchi, M., Miyadera, K., Uemura, K., et al. (1994) · Nature · doi:10.1038/368198a0 · Cited by 350 · see citing works
Discovery and Directed Evolution of a Glyphosate Tolerance Gene
Castle, L. A., Siehl, D. L., Gorton, R., et al. (2004) · Science · doi:10.1126/science.1096770 · Cited by 328 · see citing works
Robustness, evolvability, and neutrality
Wagner, A. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.01.063 · Cited by 317 · see citing works
Kuznetsova, E., Proudfoot, M., González, C. F., Brown, G., Omelchenko, M. V., Borozan, I., Carmel, L., Wolf, Y. I., Mori, H., Savchenko, A. V., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605449200 · Cited by 310 · see citing works
The altered evolutionary trajectories of gene duplicates
Lynch, M., & Katju, V. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.09.001 · Cited by 305 · see citing works
Aharoni, A., Gaidukov, L., Yagur, S., Toker, L., Silman, I., & Tawfik, D. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536901100 · Cited by 289 · see citing works
Self-citationDesign and Evolution of New Catalytic Activity with an Existing Protein Scaffold
Park, H., Nam, S., Lee, J. K., et al. (2006) · Science · doi:10.1126/science.1118953 · Cited by 285 · see citing works
Afriat‐Jurnou, L., Roodveldt, C., Manco, G., & Tawfik, D. S. (2006) · Biochemistry · doi:10.1021/bi061268r · Cited by 280 · see citing works
Self-citationAnalyzing antibody specificity with whole proteome microarrays
Michaud, G. A., Salcius, M., Zhou, F. X., Bangham, R., Bonin, J., Guo, H., Snyder, M. P., Predki, P. F., & Schweitzer, B. I. (2003) · Nature Biotechnology · doi:10.1038/nbt910 · Cited by 276 · see citing works
Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities
Janssen, D. B., Dinkla, I. J. T., Poelarends, G. J., & Terpstra, P. (2005) · Environmental Microbiology · doi:10.1111/j.1462-2920.2005.00966.x · Cited by 270 · see citing works
Carbon−Carbon Bonds by Hydrolytic Enzymes
Branneby, C., Carlqvist, P., Magnusson, A. O., et al. (2002) · Journal of the American Chemical Society · doi:10.1021/ja028056b · Cited by 263 · see citing works
Minimalist Active‐Site Redesign: Teaching Old Enzymes New Tricks
Toscano, M. D., Woycechowsky, K. J., & Hilvert, D. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200604205 · Cited by 262 · see citing works
Gene sharing by delta-crystallin and argininosuccinate lyase.
Piatigorsky, J., O’Brien, W. E., Norman, B., Kalumuck, K. E., Wistow, G. J., Borrás, T., Nickerson, J. M., & Wawrousek, E. F. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.10.3479 · Cited by 258 · see citing works
Structure-based activity prediction for an enzyme of unknown function
Hermann, J. C., Martí‐Arbona, R., Fedorov, A. A., Fedorov, E. V., Almo, S. C., Shoichet, B. K., & Raushel, F. M. (2007) · Nature · doi:10.1038/nature05981 · Cited by 256 · see citing works
Enhancing catalytic promiscuity for biocatalysis
Kazlauskas, R. J. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.02.008 · Cited by 251 · see citing works
Selenosubtilisin as a glutathione peroxidase mimic
Wu, Z. P., & Hilvert, D. (1990) · Journal of the American Chemical Society · doi:10.1021/ja00170a043 · Cited by 247 · see citing works
The new mutation theory of phenotypic evolution
Nei, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703349104 · Cited by 244 · see citing works
Selection and evolution of enzymes from a partially randomized non-catalytic scaffold
Seelig, B., & Szostak, J. W. (2007) · Nature · doi:10.1038/nature06032 · Cited by 236 · see citing works
Evolution of enzyme superfamilies
Glasner, M. E., Gerlt, J. A., & Babbitt, P. C. (2006) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2006.08.012 · Cited by 232 · see citing works
Gaidukov, L., & Tawfik, D. S. (2005) · Biochemistry · doi:10.1021/bi050862i · Cited by 223 · see citing works
Self-citationGreenspan, R. J. (2001) · Nature Reviews Genetics · doi:10.1038/35072018 · Cited by 222 · see citing works
Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases
Allali‐Hassani, A., Pan, P. W., Dombrovski, L., Najmanovich, R., Tempel, W., Dong, A., Loppnau, P., Martin, F. A., Thonton, J., Edwards, A. M., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050097 · Cited by 217 · see citing works
Diversifying Carotenoid Biosynthetic Pathways by Directed Evolution
Umeno, D., Tobias, A. V., & Arnold, F. H. (2005) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.69.1.51-78.2005 · Cited by 216 · see citing works
Chemical Mutation of Enzyme Active Sites
Kaiser, E. T., & Lawrence, D. S. (1984) · Science · doi:10.1126/science.6238407 · Cited by 211 · see citing works
HIV-1 Proviral DNA Excision Using an Evolved Recombinase
Sarkar, I., Hauber, I., Hauber, J., et al. (2007) · Science · doi:10.1126/science.1141453 · Cited by 208 · see citing works
Plasticity of the cis-Regulatory Input Function of a Gene
Mayo, A., Setty, Y., Shavit, S., Zaslaver, A., & Alon, U. S. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040045 · Cited by 197 · see citing works
Collins, C. H., Leadbetter, J. R., & Arnold, F. H. (2006) · Nature Biotechnology · doi:10.1038/nbt1209 · Cited by 190 · see citing works
Hartley, C. J., Newcomb, R. D., Russell, R. J. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509590103 · Cited by 186 · see citing works
Lee, Y.-N., Nechushtan, H., Figov, N., & Razin, E. (2004) · Immunity · doi:10.1016/s1074-7613(04)00020-2 · Cited by 184 · see citing works
The Histidine 115-Histidine 134 Dyad Mediates the Lactonase Activity of Mammalian Serum Paraoxonases
Khersonsky, O., & Tawfik, D. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512594200 · Cited by 182 · see citing works
Self-citationMatsumura, I., & Ellington, A. D. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4259 · Cited by 180 · see citing works
Lipase catalysed Michael addition of secondary amines to acrylonitrile
Torre, O., Alfonso, I., & Gotor, V. (2004) · Chemical Communications · doi:10.1039/b402244k · Cited by 180 · see citing works
O'Brie, P. J., & Herschlag, D. (2001) · Biochemistry · doi:10.1021/bi0028892 · Cited by 177 · see citing works
Multicopy Suppression Underpins Metabolic Evolvability
Patrick, W. M., Quandt, E. M., Swartzlander, D. B., & Matsumura, I. (2007) · Molecular Biology and Evolution · doi:10.1093/molbev/msm204 · Cited by 177 · see citing works
Off-the-shelf proteins that rival tailor-made antibodies as catalysts
Hollfelder, F., Kirby, A. J., & Tawfik, D. S. (1996) · Nature · doi:10.1038/383060a0 · Cited by 175 · see citing works
Self-citationJürgens, C., Strom, A. M., Wegener, D., Hettwer, S., Wilmanns, M., & Sterner, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160255397 · Cited by 170 · see citing works
Schmidt, D. M. Z., Mundorff, E. C., Dojka, M., Bermudez, E., Ness, J. E., Govindarajan, S., Babbitt, P. C., Minshull, J., & Gerlt, J. A. (2003) · Biochemistry · doi:10.1021/bi034769a · Cited by 170 · see citing works
Acetylation of human serum albumin by p-nitrophenyl acetate
Means, G. E., & Bender, M. L. (1975) · Biochemistry · doi:10.1021/bi00693a031 · Cited by 169 · see citing works
Structural plasticity broadens the specificity of an engineered protease
Bone, R. F., Silen, J. L., & Agard, D. A. (1989) · Nature · doi:10.1038/339191a0 · Cited by 165 · see citing works
Varadarajan, N., Gam, J., Olsen, M. J., Georgiou, G., & Iverson, B. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500063102 · Cited by 164 · see citing works
Piatigorsky, J. (2007) · Harvard University Press eBooks · doi:10.4159/9780674042124 · Cited by 161 · see citing works
Lancet, D., Sadovsky, E., & Seidemann, E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3715 · Cited by 160 · see citing works
Latent evolutionary potentials under the neutral mutational drift of an enzyme
Amitai, G., Gupta, T., & Tawfik, D. S. (2007) · HFSP journal · doi:10.2976/1.2739115/10.2976/1 · Cited by 160 · see citing works
Self-citationBarlow, M., & Hall, B. G. (2002) · Journal of Molecular Evolution · doi:10.1007/s00239-002-2328-y · Cited by 158 · see citing works
Yang, K., & Metcalf, W. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400664101 · Cited by 158 · see citing works
Lamble, H. J., Heyer, N. I., Bull, S. D., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305818200 · Cited by 150 · see citing works
Watts, K. T., Mijts, B. N., Lee, P. C., Manning, A. J., & Schmidt‐Dannert, C. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.10.008 · Cited by 150 · see citing works
Exploring the Active‐Site of a Rationally Redesigned Lipase for Catalysis of Michael‐Type Additions
Carlqvist, P., Humble, M. S., Branneby, C., et al. (2004) · ChemBioChem · doi:10.1002/cbic.200400213 · Cited by 145 · see citing works
Lodeiro, S., Xiong, Q., Wilson, W. K., et al. (2007) · Journal of the American Chemical Society · doi:10.1021/ja073133u · Cited by 145 · see citing works
Origin of rate accelerations in an enzyme model: the p-nitrophenyl ester syndrome
Menger, F. M., & Ladika, M. (1987) · Journal of the American Chemical Society · doi:10.1021/ja00244a047 · Cited by 145 · see citing works
Predicting the evolution of antibiotic resistance genes
Hall, B. G. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro888 · Cited by 143 · see citing works
James, L. C., & Tawfik, D. S. (2003) · Protein Science · doi:10.1110/ps.03172703 · Cited by 143 · see citing works
Self-citationConformational variability of matrix metalloproteinases: Beyond a single 3D structure
Bertini, I., Calderone, V., Cosenza, M., Fragai, M., Lee, Y., Luchinat, C., Mangani, S., Terni, B., & Turano, P. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407106102 · Cited by 141 · see citing works
Galvão, T. C., & de Lorenzo, V. (2005) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2005.12.002 · Cited by 140 · see citing works
Genetic Constraints on Protein Evolution
Camps, M., Herman, A., Loh, E., & Loeb, L. A. (2007) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230701597642 · Cited by 140 · see citing works
Roodveldt, C., & Tawfik, D. S. (2005) · Biochemistry · doi:10.1021/bi051021e · Cited by 134 · see citing works
Self-citationCatalytic Promiscuity and the Divergent Evolution of DNA Repair Enzymes
O’Brien, P. (2006) · Chemical Reviews · doi:10.1021/cr040481v · Cited by 130 · see citing works
Man-made enzymes — from design to in vitro compartmentalisation
Griffiths, A. D., & Tawfik, D. S. (2000) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(00)00109-9 · Cited by 129 · see citing works
Self-citationScannell, D. R., & Wolfe, K. H. (2007) · Genome Research · doi:10.1101/gr.6341207 · Cited by 129 · see citing works
Liu, D., Lepore, B. W., Petsko, G. A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505255102 · Cited by 124 · see citing works
Transforming Carbonic Anhydrase into Epoxide Synthase by Metal Exchange
Fernández‐Gacio, A., Codina, A., Fastrez, J., et al. (2006) · ChemBioChem · doi:10.1002/cbic.200600127 · Cited by 120 · see citing works
Evolution favors protein mutational robustness in sufficiently large populations
Bloom, J. D., Lu, Z., Chen, D., Raval, A., Venturelli, O. S., & Arnold, F. H. (2007) · BMC Biology · doi:10.1186/1741-7007-5-29 · Cited by 119 · see citing works
Pocker, Y., & Stone, J. T. (1965) · Journal of the American Chemical Society · doi:10.1021/ja00951a049 · Cited by 119 · see citing works
The Structure of Human SULT1A1 Crystallized with Estradiol
Gamage, N. U., Tsvetanov, S., Duggleby, R. G., McManus, M. E., & Martin, J. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508289200 · Cited by 116 · see citing works
O'Brie, P. J., & Herschlag, D. (1998) · Journal of the American Chemical Society · doi:10.1021/ja983390m · Cited by 114 · see citing works
Palmer, D. R. J., Garrett, J. B., Sharma, V., Meganathan, R., Babbitt, P. C., & Gerlt, J. A. (1999) · Biochemistry · doi:10.1021/bi990140p · Cited by 114 · see citing works
Cohen, H. M., Tawfik, D. S., & Griffiths, A. D. (2004) · Protein Engineering Design and Selection · doi:10.1093/protein/gzh001 · Cited by 110 · see citing works
Self-citationYu, H., Liu, J., Böck, A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408574200 · Cited by 109 · see citing works
Conversion of a PLP-Dependent Racemase into an Aldolase by a Single Active Site Mutation
Seebeck, F. P., & Hilvert, D. (2003) · Journal of the American Chemical Society · doi:10.1021/ja036707d · Cited by 109 · see citing works
Amitai, G., Gaidukov, L., Adani, R., et al. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05198.x · Cited by 108 · see citing works
Directed Evolution of the Promiscuous Esterase Activity of Carbonic Anhydrase II
Gould, S. M., & Tawfik, D. S. (2005) · Biochemistry · doi:10.1021/bi0475471 · Cited by 107 · see citing works
Self-citationFlexibility in a Gene Network Affecting a Simple Behavior in Drosophila melanogaster
van Swinderen, B., & Greenspan, R. J. (2005) · Genetics · doi:10.1534/genetics.104.032631 · Cited by 101 · see citing works
Escherichia coli L-asparaginase. Catalytic activity and subunit nature
Jackson, R. C., & Handschumacher, R. E. (1970) · Biochemistry · doi:10.1021/bi00820a013 · Cited by 100 · see citing works
Blum, M., Löhr, F., Richardt, A., et al. (2006) · Journal of the American Chemical Society · doi:10.1021/ja061887n · Cited by 97 · see citing works
A Quantitative Index of Substrate Promiscuity
Nath, A., & Atkins, W. M. (2007) · Biochemistry · doi:10.1021/bi701448p · Cited by 97 · see citing works
Identifying Latent Enzyme Activities: Substrate Ambiguity within Modern Bacterial Sugar Kinases
Miller, B. G., & Raines, R. T. (2004) · Biochemistry · doi:10.1021/bi049424m · Cited by 93 · see citing works
Occurrence of a putative ancient‐like isomerase involved in histidine and tryptophan biosynthesis
Barona‐Gómez, F., & Hodgson, D. A. (2003) · EMBO Reports · doi:10.1038/sj.embor.embor771 · Cited by 93 · see citing works
James, L. C., & Tawfik, D. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500909102 · Cited by 93 · see citing works
Self-citationBone, R. F., Frank, D., Kettner, C. A., et al. (1989) · Biochemistry · doi:10.1021/bi00445a015 · Cited by 89 · see citing works
Adaptive evolution after gene duplication
Hughes, A. L. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02755-5 · Cited by 89 · see citing works
Ligand selectivity and competition between enzymes in silico
Macchiarulo, A., Nobeli, I., & Thornton, J. M. (2004) · Nature Biotechnology · doi:10.1038/nbt999 · Cited by 89 · see citing works
Phosphotriesterase: An Enzyme in Search of Its Natural Substrate
Raushel, F. M., & Holden, H. M. (2000) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470123201.ch2 · Cited by 86 · see citing works
Taylor, E. A., Garrett, J. B., Thoden, J. B., et al. (2003) · Biochemistry · doi:10.1021/bi035815+ · Cited by 86 · see citing works
Targeting platelet-derived endothelial cell growth factor/thymidine phosphorylase for cancer therapy
Liekens, S., Bronckaers, A., Pérez‐Pérez, M., et al. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.05.008 · Cited by 83 · see citing works
Theodossis, A., Walden, H., Westwick, E. J., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407702200 · Cited by 82 · see citing works
Perona, J. J., & Martin, A. M. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1315 · Cited by 82 · see citing works
A High‐Throughput‐Screening Method for Determining the Synthetic Activity of Hydrolases
Konarzycka‐Bessler, M., & Bornscheuer, U. T. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200390365 · Cited by 80 · see citing works
Creation of the first anomeric d / l -sugar kinase by means of directed evolution
Hoffmeister, D., Yang, J., Liu, L., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100.23.13184 · Cited by 79 · see citing works
Kotik-Kogan, O., Moor, N. A., Tworowski, D., et al. (2005) · Structure · doi:10.1016/j.str.2005.08.013 · Cited by 77 · see citing works
Hou, L., Honaker, M. T., Shireman, L. M., Balogh, L. M., Roberts, A. G., Ng, K.-C., Nath, A., & Atkins, W. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700868200 · Cited by 77 · see citing works
Joerger, A. C., Mayer, S., & Fersht, A. R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0531477100 · Cited by 76 · see citing works
Henn-Sax, M., Thoma, R., Schmidt, S., et al. (2002) · Biochemistry · doi:10.1021/bi026092h · Cited by 74 · see citing works
Catrina, I. E., O’Brien, P., Purcell, J., et al. (2007) · Journal of the American Chemical Society · doi:10.1021/ja069111+ · Cited by 74 · see citing works
Brevet, A., Plateau, P., Çırakoğlu, B., et al. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33321-0 · Cited by 73 · see citing works
Tremblay, L. W., Dunaway‐Mariano, D., & Allen, K. N. (2006) · Biochemistry · doi:10.1021/bi051842j · Cited by 72 · see citing works
Reshetnikova, L. S., Moor, N. A., Lavrik, O. I., & Vassylyev, D. G. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2617 · Cited by 70 · see citing works
A Despecialization Step Underlying Evolution of a Family of Serine Proteases
Wouters, M. A., Liu, K., Riek, P., & Husain, A. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00308-3 · Cited by 69 · see citing works
Boschi‐Müller, S., Müller, S., DORSSELAER, A. V., et al. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01377-5 · Cited by 68 · see citing works
Understanding Promiscuous Amidase Activity of an Esterase from Bacillus subtilis
Kourist, R., Bartsch, S., Fransson, L. M. L., et al. (2007) · ChemBioChem · doi:10.1002/cbic.200700521 · Cited by 68 · see citing works
Hsu, C., Hong, Z., Wada, M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504033102 · Cited by 67 · see citing works
Rothman, S. C., & Kirsch, J. F. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00095-0 · Cited by 67 · see citing works
Creation of the first anomeric D/L-sugar kinase by means of directed evolution
Hoffmeister, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235011100 · Cited by 66 · see citing works
Wang, S. C., Person, M. D., William H. Johnson, et al. (2003) · Biochemistry · doi:10.1021/bi034598+ · Cited by 64 · see citing works
Engineering Steroid 5β-Reductase Activity into Rat Liver 3α-Hydroxysteroid Dehydrogenase
Jez, J. M., & Penning, T. M. (1998) · Biochemistry · doi:10.1021/bi980294p · Cited by 63 · see citing works
Lü, X., Li, L., Wu, R., et al. (2006) · Biochemistry · doi:10.1021/bi051591e · Cited by 63 · see citing works
A Comparison of Directed Evolution Approaches Using the β-Glucuronidase Model System
Rowe, L. A., Geddie, M. L., Alexander, O. B., & Matsumura, I. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00972-0 · Cited by 63 · see citing works
Analysis of active‐site amino‐acid residues of human serum paraoxonase using competitive substrates
Yeung, D. T., Lenz, D. E., & Cerasoli, D. M. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.04646.x · Cited by 63 · see citing works
[30] Soluble methane monooxygenase from Methylococcus capsulatus bath
Pilkington, S. J., & Dalton, H. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)88032-6 · Cited by 63 · see citing works
Pettersson, P. L., Johansson, A.-S., & Mannervik, B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204485200 · Cited by 62 · see citing works
A structural model of latent evolutionary potentials underlying neutral networks in proteins
Wroe, R., Chan, H. S., & Bornberg‐Bauer, E. (2007) · HFSP journal · doi:10.2976/1.2739116/10.2976/1 · Cited by 62 · see citing works
Künzler, D. E., Sasso, S., Gamper, M., Hilvert, D., & Kast, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506883200 · Cited by 61 · see citing works
Natural history as a predictor of protein evolvability
O'Loughlin, T. L. (2006) · Protein Engineering Design and Selection · doi:10.1093/protein/gzl029 · Cited by 60 · see citing works
Evolution of Enzymes for the Metabolism of New Chemical Inputs into the Environment
Wackett, L. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400014200 · Cited by 59 · see citing works
3,4‐Dihydrocoumarin hydrolase with haloperoxidase activity from Acinetobacter calcoaceticus F46
Kataoka, M., Honda, K., & Shimizu, S. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.00889.x · Cited by 55 · see citing works
Wang, S. C., Johnson, W. H., & Whitman, C. P. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0370948 · Cited by 55 · see citing works
Enzyme-catalysed siloxane bond formation
Bassindale, A. R., Brandstadt, K. F., Lane, T. H., et al. (2003) · Journal of Inorganic Biochemistry · doi:10.1016/s0162-0134(03)00177-6 · Cited by 55 · see citing works
Structural plasticity of an aminoacyl-tRNA synthetase active site
Turner, J. M., Graziano, J. J., Spraggon, G., & Schultz, P. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601756103 · Cited by 55 · see citing works
Vick, J. E., Schmidt, D. M. Z., & Gerlt, J. A. (2005) · Biochemistry · doi:10.1021/bi050963g · Cited by 51 · see citing works
Li, C., Hassler, M. R., & Bugg, T. D. H. (2007) · ChemBioChem · doi:10.1002/cbic.200700428 · Cited by 51 · see citing works
Fluorophoric Assay for the High-Throughput Determination of Amidase Activity
Henke, E., & Bornscheuer, U. T. (2002) · Analytical Chemistry · doi:10.1021/ac0258610 · Cited by 51 · see citing works
Creation of a Shikimate Pathway Variant
Ran, N., Draths, K. M., & Frost, J. W. (2004) · Journal of the American Chemical Society · doi:10.1021/ja049730n · Cited by 47 · see citing works
Yasutake, Y., Yao, M., Sakai, N., et al. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.09.035 · Cited by 46 · see citing works
Reconstitution of a Defunct Glycolytic Pathway via Recruitment of Ambiguous Sugar Kinases
Miller, B. G., & Raines, R. T. (2005) · Biochemistry · doi:10.1021/bi0506268 · Cited by 45 · see citing works
Griswold, K. E., Aiyappan, N. S., Iverson, B. L., et al. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.09.012 · Cited by 44 · see citing works
Leopoldseder, S., Claren, J., Jürgens, C., & Sterner, R. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.01.062 · Cited by 43 · see citing works
Yew, W. S., Akana, J., Wise, E. L., et al. (2005) · Biochemistry · doi:10.1021/bi047815v · Cited by 42 · see citing works
D ‐Amino acids and D ‐Tyr‐tRNATyr deacylase: stereospecificity of the translation machine revisited
Yang, H., Zheng, G., Peng, X., Qiang, B., & Yuan, J. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00858-5 · Cited by 42 · see citing works
Varga, J. M., Kalchschmid, G., Klein, G., & Fritsch, P. O. (1991) · Molecular Immunology · doi:10.1016/0161-5890(91)90133-5 · Cited by 40 · see citing works
The pepsin-catalyzed hydrolysis of sulfite esters
Reid, T. W., & Fahrney, D. (1967) · Journal of the American Chemical Society · doi:10.1021/ja00991a072 · Cited by 40 · see citing works
Hall, B. G. (1999) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1999.tb13542.x · Cited by 37 · see citing works
Rothman, S. C., Voorhies, M., & Kirsch, J. F. (2004) · Protein Science · doi:10.1110/ps.03117204 · Cited by 36 · see citing works
Poelarends, G. J., Serrano, H., Johnson, W. H., et al. (2004) · Journal of the American Chemical Society · doi:10.1021/ja044304n · Cited by 36 · see citing works
Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9
Delmas, J., Robin, F., Carvalho, F. A., et al. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.2.731-738.2006 · Cited by 36 · see citing works
Diversification and Specialization of HIV Protease Function During In Vitro Evolution
O'Loughlin, T. L. (2006) · Molecular Biology and Evolution · doi:10.1093/molbev/msj098 · Cited by 36 · see citing works
A biological cosmos of parallel universes: Does protein structural plasticity facilitate evolution?
Meier, S., & Özbek, S. (2007) · BioEssays · doi:10.1002/bies.20661 · Cited by 34 · see citing works
Larion, M., Moore, L. B., Thompson, S. M., et al. (2007) · Biochemistry · doi:10.1021/bi700924d · Cited by 34 · see citing works
Modification of .alpha.-chymotrypsin by methyl p-nitrobenzenesulfonate
Nakagawa, Y., & Bender, M. L. (1969) · Journal of the American Chemical Society · doi:10.1021/ja01034a068 · Cited by 32 · see citing works
Vick, J. E., & Gerlt, J. A. (2007) · Biochemistry · doi:10.1021/bi7019063 · Cited by 32 · see citing works
Wei, C.-L., Yang, Y.-B., Deng, C.-H., et al. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.12.8873-8880.2005 · Cited by 31 · see citing works
Engineering a rare-cutting restriction enzyme: genetic screening and selection of NotI variants
Samuelson, J. C. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj483 · Cited by 31 · see citing works
Kurakin, A. V. (2007) · Journal of Molecular Recognition · doi:10.1002/jmr.839 · Cited by 30 · see citing works
Chow, M. A., McElroy, K. E., Corbett, K. D., Berger, J. M., & Kirsch, J. F. (2004) · Biochemistry · doi:10.1021/bi0487544 · Cited by 29 · see citing works
Bakker, M., van Rantwijk, F., & Sheldon, R. A. (2002) · Canadian Journal of Chemistry · doi:10.1139/v02-082 · Cited by 29 · see citing works
O’Hare, H. M., Huang, F., Holding, A. N., Choroba, O. W., & Spencer, J. B. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.05.018 · Cited by 28 · see citing works
Catechol Oxidase Activity of Di-Cu2+-Substituted Aminopeptidase from Streptomyces griseus
da Silva, G. F. Z., & Ming, L. (2005) · Journal of the American Chemical Society · doi:10.1021/ja056034u · Cited by 28 · see citing works
Changing the recognition specificity of a DNA-methyltransferase by in vitro evolution
Tímár, E. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh724 · Cited by 28 · see citing works
In search of the limits of evolution
Kondrashov, F. A. (2004) · Nature Genetics · doi:10.1038/ng0105-9 · Cited by 27 · see citing works
Adami, C. (2006) · Science · doi:10.1126/science.1126559 · Cited by 23 · see citing works
Arima, J., Uesugi, Y., Iwabuchi, M., et al. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.11.7229-7235.2005 · Cited by 22 · see citing works
Domenech, J., & Ferrer, J. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2006.08.024 · Cited by 21 · see citing works
Poelarends, G. J., Serrano, H., Johnson, W. H., et al. (2005) · Biochemistry · doi:10.1021/bi050296r · Cited by 21 · see citing works
Rabbit Serum Albumin Hydrolyzes the Carbamate Carbaryl
Sogorb, M. A., Carrera, V., Benabent, M., et al. (2002) · Chemical Research in Toxicology · doi:10.1021/tx015577o · Cited by 17 · see citing works
Mot, R., de Schrijver, A., Schoofs, G., et al. (2003) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(03)00452-x · Cited by 15 · see citing works
Promiscuous Catalysis by the Tetrahymena Group I Ribozyme
Forconi, M., & Herschlag, D. (2005) · Journal of the American Chemical Society · doi:10.1021/ja050180i · Cited by 14 · see citing works
Varga, J. M., Kalchschmid, G., Klein, G., & Fritsch, P. O. (1991) · Molecular Immunology · doi:10.1016/0161-5890(91)90134-6 · Cited by 13 · see citing works
The Role of Inhibition in Enzyme Evolution
McLoughlin, S. Y., & Ollis, D. L. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.03.031 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Enzyme promiscuity: A mechanistic and evolutionary perspective
Tawfik, O. K. A. D. S. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-030409-143718 · Cited by 1,355 · see citing works
Adaptive laboratory evolution—Principles and applications for biotechnology
Dragosits, M., & Mattanovich, D. (2013) · Microbial Cell Factories · doi:10.1186/1475-2859-12-64 · Cited by 827 · see citing works
The Role of Conformational Dynamics and Allostery in Modulating Protein Evolution
Campitelli, P., Modi, T., Kumar, S., & Ozkan, S. B. (2020) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-052118-115517 · Cited by 190 · see citing works
Origins of specificity and promiscuity in metabolic networks
Carbonell, P., Lecointre, G., & Faulon, J.-L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.274050 · Cited by 87 · see citing works
Opportunities for merging chemical and biological synthesis
Wallace, S., & Balskus, E. P. (2014) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.03.006 · Cited by 86 · see citing works
Weber, N., Halpin, C., Hannah, L. C., Jez, J. M., Kough, J., & Parrott, W. (2012) · Plant Physiology · doi:10.1104/pp.112.204271 · Cited by 78 · see citing works
The metabolic network of the last bacterial common ancestor
Xavier, J. C., Gerhards, R. E., Wimmer, J. L. E., Brueckner, J., Tria, F. D. K., & Martin, W. F. (2021) · Communications Biology · doi:10.1038/s42003-021-01918-4 · Cited by 59 · see citing works
Challenges in the computational design of proteins
Suárez, M., & Jaramillo, A. (2009) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0508.focus · Cited by 59 · see citing works
- Authors
- Khersonsky, O., Roodveldt, C., & Tawfik, D. S.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Tawfik, Dan S
- Venue
- Current Opinion in Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 10
- Issue
- 5
- Pages
- 498-508
- ISSN
- 1367-5931 (ISSN-L)
- OpenAlex
- W2135900956
- Cited by
- 641
- References
- 194
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 34 · 2023: 15 · 2022: 27 · 2021: 20 · 2020: 29 · 2019: 25 · 2018: 30 · 2017: 31 · 2016: 27 · 2015: 31 · 2014: 29 · 2013: 33 · 2012: 41
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Science and Technology, Ministry of Science and Technology, India
- Israel Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Keywords
- enzyme promiscuity, catalytic promiscuity, enzyme evolution, latent enzyme activity, enzyme specificity, enzyme superfamilies, enzyme families, enzyme mechanism
- MeSH terms
- Animals, Catalysis, Enzyme Activation, Enzymes, Humans, Substrate Specificity, Evolution, Molecular
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review