• Savile, C. K. et al. Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture. Science 329, 305–309 (2010).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Huffman, M. A. et al. Design of an in vitro biocatalytic cascade for the manufacture of islatravir. Science 366, 1255–1259 (2019). erratum 368, eabc1954 (2020).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Schober, M. et al. Chiral synthesis of LSD1 inhibitor GSK2879552 enabled by directed evolution of an imine reductase. Nat. Catal. 2, 909–915 (2019).

    CAS 
    Article 

    Google Scholar
     

  • Devine, P. N. et al. Extending the application of biocatalysis to meet the challenges of drug development. Nat. Rev. Chem. 2, 409–421 (2018).

    Article 

    Google Scholar
     

  • Turner, N. J. Directed evolution drives the next generation of biocatalysts. Nat. Chem. Biol. 5, 567–573 (2009).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Bornscheuer, U. T. et al. Engineering the third wave of biocatalysis. Nature 485, 185–194 (2012).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Zeymer, C. & Hilvert, D. Directed evolution of protein catalysts. Annu. Rev. Biochem. 87, 131–157 (2018).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Arnold, F. H. Directed evolution: bringing new chemistry to life. Angew. Chem. Int. Ed. 57, 4143–4148 (2018).

    CAS 
    Article 

    Google Scholar
     

  • Qu, G., Li, A., Acevedo-Rocha, C. G., Sun, Z. & Reetz, M. T. The crucial role of methodology development in directed evolution of selective enzymes. Angew. Chem. Int. Ed. 59, 13204–13231 (2020).

    CAS 
    Article 

    Google Scholar
     

  • Fernandez-Gacio, A., Uguen, M. & Fastrez, J. Phage display as a tool for the directed evolution of enzymes. Trends Biotechnol. 21, 408–414 (2003).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Becker, S., Schmoldt, H. U., Adams, T. M., Wilhelm, S. & Kolmar, H. Ultra-high-throughput screening based on cell-surface display and fluorescence-activated cell sorting for the identification of novel biocatalysts. Curr. Opin. Biotechnol. 15, 323–329 (2004).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Agresti, J. J. et al. Ultrahigh-throughput screening in drop-based microfluidics for directed evolution. Proc. Natl Acad. Sci. USA 107, 4004–4009 (2010).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Debon, A. et al. Ultrahigh-throughput screening enables efficient single-round oxidase remodelling. Nat. Catal. 2, 740–747 (2019).

    CAS 
    Article 

    Google Scholar
     

  • Esvelt, K. M., Carlson, J. C. & Liu, D. R. A system for the continuous directed evolution of biomolecules. Nature 472, 499–503 (2011).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Bryson, D. I. et al. Continuous directed evolution of aminoacyl-tRNA synthetases. Nat. Chem. Biol. 13, 1253–1260 (2017).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Ravikumar, A., Arzumanyan, G. A., Obadi, M. K. A., Javanpour, A. A. & Liu, C. C. Scalable, continuous evolution of genes at mutation rates above genomic error thresholds. Cell 175, 1946–1957 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Zhang, R. K. et al. Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3 C–H functionalization. Nature 565, 67–72 (2018).

    ADS 
    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Chen, K., Huang, X., Kan, S. B. J., Zhang, R. K. & Arnold, F. H. Enzymatic construction of highly strained carbocycles. Science 360, 71–75 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Biegasiewicz, K. F. et al. Photoexcitation of flavoenzymes enables a stereoselective radical cyclization. Science 364, 1166–1169 (2019).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Ji, P., Park, J., Gu, Y., Clark, D. S. & Hartwig, J. F. Abiotic reduction of ketones with silanes catalysed by carbonic anhydrase through an enzymatic zinc hydride. Nat. Chem. 13, 312–318 (2021).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Kiss, G., Celebi-Olcum, N., Moretti, R., Baker, D. & Houk, K. N. Computational enzyme design. Angew. Chem. Int. Ed. 52, 5700–5725 (2013).

    CAS 
    Article 

    Google Scholar
     

  • Hilvert, D. Design of protein catalysts. Annu. Rev. Biochem. 82, 447–470 (2013).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Baker, D. An exciting but challenging road ahead for computational enzyme design. Protein Sci. 19, 1817–1819 (2010).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Jeschek, M. et al. Directed evolution of artificial metalloenzymes for in vivo metathesis. Nature 537, 661–665 (2016).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Zhao, J. et al. Genetic engineering of an artificial metalloenzyme for transfer hydrogenation of a self-immolative substrate in Escherichia coli’s periplasm. J. Am. Chem. Soc. 140, 13171–13175 (2018).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Rebelein, J. G. & Ward, T. R. In vivo catalyzed new-to-nature reactions. Curr. Opin. Biotechnol. 53, 106–114 (2018).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hyster, T. K., Knorr, L., Ward, T. R. & Rovis, T. Biotinylated Rh(III) complexes in engineered streptavidin for accelerated asymmetric C–H activation. Science 338, 500–503 (2012). Demonstration that transition metal complexes embedded in protein hosts can work in synergy with amino acid side chains to accelerate a challenging C–H activation process.

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Bhagi-Damodaran, A. et al. Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases. Nat. Chem. 9, 257–263 (2017).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Yeung, N. et al. Rational design of a structural and functional nitric oxide reductase. Nature 462, 1079–1082 (2009).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Mirts, E. N., Petrik, I. D., Hosseinzadeh, P., Nilges, M. J. & Lu, Y. A designed heme-[4Fe–4S] metalloenzyme catalyzes sulfite reduction like the native enzyme. Science 361, 1098–1101 (2018). This study shows how the introduction of new functional elements into metalloproteins can generate artificial enzymes for challenging chemical tranformations that have thus far eluded synthetic catalysts.

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Hill, R. B., Raleigh, D. P., Lombardi, A. & DeGrado, W. F. De novo design of helical bundles as models for understanding protein folding and function. Acc. Chem. Res. 33, 745–754 (2000).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Koder, R. L. & Dutton, P. L. Intelligent design: the de novo engineering of proteins with specified functions. Dalton Trans. 25, 3045–3051 (2006).

    Article 
    CAS 

    Google Scholar
     

  • Faiella, M. et al. An artificial di-iron oxo-protein with phenol oxidase activity. Nat. Chem. Biol. 5, 882–884 (2009).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Smith, B. A. & Hecht, M. H. Novel proteins: from fold to function. Curr. Opin. Chem. Biol. 15, 421–426 (2011).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Zastrow, M. L., Peacock, A. F., Stuckey, J. A. & Pecoraro, V. L. Hydrolytic catalysis and structural stabilization in a designed metalloprotein. Nat. Chem. 4, 118–123 (2011).

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Stenner, R., Steventon, J. W., Seddon, A. & Anderson, J. L. R. A de novo peroxidase is also a promiscuous yet stereoselective carbene transferase. Proc. Natl Acad. Sci. USA 117, 1419–1428 (2020).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Chino, M. et al. A de novo heterodimeric Due Ferri protein minimizes the release of reactive intermediates in dioxygen-dependent oxidation. Angew. Chem. Int. Ed. 56, 15580–15583 (2017).

    CAS 
    Article 

    Google Scholar
     

  • Lombardi, A., Pirro, F., Maglio, O., Chino, M. & DeGrado, W. F. De novo design of four-helix bundle metalloproteins: one scaffold, diverse reactivities. Acc. Chem. Res. 52, 1148–1159 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Reig, J. A. et al. Alteration of the oxygen-dependent reactivity of de novo Due Ferri proteins. Nat. Chem. 4, 900–906 (2012). Demonstration that the catalytic function of de novo Due Ferri proteins can be altered through rational reprogramming of the metal coordination environment.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Salgado, E. N., Faraone-Mennella, J. & Tezcan, F. A. Controlling protein–protein interactions through metal coordination: assembly of a 16-helix bundle protein. J. Am. Chem. Soc. 129, 13374–13375 (2007).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Der, B. S. et al. Metal-mediated affinity and orientation specificity in a computationally designed protein homodimer. J. Am. Chem. Soc. 134, 375–385 (2012).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Der, B. S., Edwards, D. R. & Kuhlman, B. Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering. Biochemistry 51, 3933–3940 (2012).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Studer, S. et al. Evolution of a highly active and enantiospecific metalloenzyme from short peptides. Science 362, 1285–1288 (2018). This study uses a combination of design and evolution to transform a designed zinc-binding peptide into a globular metalloenzyme that accelerates ester hydrolysis with high efficiency.

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Basler, S. et al. Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold. Nat. Chem. 13, 231–235 (2021). In this study, a de novo metalloenzyme is engineered to accelerate an abiological hetero-Diels–Alder reaction with high specificity and a catalytic proficiency that exceeds all previously characterized Diels–Alderases.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Chin, J. W. Expanding and reprogramming the genetic code. Nature 550, 53–60 (2017).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Liu, C. C. & Schultz, P. G. Adding new chemistries to the genetic code. Annu. Rev. Biochem. 79, 413–444 (2010).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Seyedsayamdost, M. R., Xie, J., Chan, C. T. Y., Schultz, P. G. & Stubbe, J. Site-specific insertion of 3-aminotyrosine into subunit α2 of E. coli ribonucleotide reductase: direct evidence for involvement of Y730 and Y731 in radical propagation. J. Am. Chem. Soc. 129, 15060–15071 (2007).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Faraldos, J. A. et al. Probing eudesmane cation−π interactions in catalysis by aristolochene synthase with non-canonical amino acids. J. Am. Chem. Soc. 133, 13906–13909 (2011).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Wu, Y. & Boxer, S. G. A critical test of the electrostatic contribution to catalysis with noncanonical amino acids in ketosteroid isomerase. J. Am. Chem. Soc. 138, 11890–11895 (2016).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Ortmayer, M. et al. Rewiring the ‘push–pull’ catalytic machinery of a heme enzyme using an expanded genetic code. ACS Catal. 10, 2735–2746 (2020).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Ortmayer, M. et al. A noncanonical tryptophan analogue reveals an active site hydrogen bond controlling ferryl reactivity in a heme peroxidase. JACS Au 1, 913–918 (2021).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Li, J. C., Liu, T., Wang, Y., Mehta, A. P. & Schultz, P. G. Enhancing protein stability with genetically encoded noncanonical amino acids. J. Am. Chem. Soc. 140, 15997–16000 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Green, A. P., Hayashi, T., Mittl, P. R. & Hilvert, D. A chemically programmed proximal ligand enhances the catalytic properties of a heme enzyme. J. Am. Chem. Soc. 138, 11344–11352 (2016).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Zhao, J., Burke, A. J. & Green, A. P. Enzymes with noncanonical amino acids. Curr. Opin. Chem. Biol. 55, 136–144 (2020).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Burke, A. J. et al. Design and evolution of an enzyme with a non-canonical organocatalytic mechanism. Nature 570, 219–223 (2019). Demonstrates how introducing noncanonical amino acids can expand the chemical reactivity and catalytic mechanisms accessible with designed enzymes.

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Bolon, D. N. & Mayo, S. L. Enzyme-like proteins by computational design. Proc. Natl Acad. Sci. USA 98, 14274–14279 (2001).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Richter, F. et al. Computational design of catalytic dyads and oxyanion holes for ester hydrolysis. J. Am. Chem. Soc. 134, 16197–16206 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Rajagopalan, S. et al. Design of activated serine-containing catalytic triads with atomic-level accuracy. Nat. Chem. Biol. 10, 386–391 (2014).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Moroz, Y. S. et al. New tricks for old proteins: single mutations in a nonenzymatic protein give rise to various enzymatic activities. J. Am. Chem. Soc. 137, 14905–14911 (2015).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Burton, A. J., Thomson, A. R., Dawson, W. M., Brady, R. L. & Woolfson, D. N. Installing hydrolytic activity into a completely de novo protein framework. Nat. Chem. 8, 837–844 (2016).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Drienovska, I., Mayer, C., Dulson, C. & Roelfes, G. A designer enzyme for hydrazone and oxime formation featuring an unnatural catalytic aniline residue. Nat. Chem. 10, 946–952 (2018). Demonstrates that the introduction of noncanonical amino acids can open up new modes of reactivity within proteins.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Mayer, C., Dulson, C., Reddem, E., Thunnissen, A. W. H. & Roelfes, G. Directed evolution of a designer enzyme featuring an unnatural catalytic amino acid. Angew. Chem. Int. Ed. 58, 2083–2087 (2019).

    CAS 
    Article 

    Google Scholar
     

  • Tramontano, A., Janda, K. D. & Lerner, R. A. Catalytic antibodies. Science 234, 1566–1570 (1986).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Wagner, J., Lerner, R. A. & Barbas, C. F. III. Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes. Science 270, 1797–1800 (1995).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Gouverneur, V. E. et al. Control of the exo and endo pathways of the Diels–Alder reaction by antibody catalysis. Science 262, 204–208 (1993).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Wentworth, P. Jr. et al. Antibody catalysis of the oxidation of water. Science 293, 1806–1811 (2001).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hsieh, L. C., Yonkovich, S., Kochersperger, L. & Schultz, P. G. Controlling chemical reactivity with antibodies. Science 260, 337–339 (1993).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hilvert, D. Critical analysis of antibody catalysis. Annu. Rev. Biochem. 69, 751–793 (2000).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Rothlisberger, D. et al. Kemp elimination catalysts by computational enzyme design. Nature 453, 190–195 (2008).

    ADS 
    PubMed 
    Article 
    CAS 

    Google Scholar
     

  • Privett, H. K. et al. Iterative approach to computational enzyme design. Proc. Natl Acad. Sci. USA 109, 3790–3795 (2012).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Jiang, L. et al. De novo computational design of retro-aldol enzymes. Science 319, 1387–1391 (2008).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Siegel, J. B. et al. Computational design of an enzyme catalyst for a stereoselective bimolecular Diels–Alder reaction. Science 329, 309–313 (2010). Computational design and experimental characterization of enzymes catalysing a bimolecular Diels–Alder reaction, an important carbon–carbon bond-forming process.

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Blomberg, R. et al. Precision is essential for efficient catalysis in an evolved Kemp eliminase. Nature 503, 418–421 (2013). Demonstrates that artificial enzymes can be evolved to accelerate elementary chemical reactions with efficiencies comparable to natural enzymes.

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Preiswerk, N. et al. Impact of scaffold rigidity on the design and evolution of an artificial Diels–Alderase. Proc. Natl Acad. Sci. USA 111, 8013–8018 (2014).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Obexer, R. et al. Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase. Nat. Chem. 9, 50–56 (2017). Ultrahigh-throughput screening facilitates the development of artificial enzymes with efficiencies comparable to natural systems.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Crawshaw, R. et al. Engineering an efficient and enantioselective enzyme for the Morita–Baylis–Hillman reaction. Nat. Chem. 14, 313–320 (2022). A demonstration that laboratory evolution of designed enzymes can deliver sophisticated active sites to accelerate complex nonbiological transformations.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Otten, R. et al. How directed evolution reshapes the energy landscape in an enzyme to boost catalysis. Science 370, 1442–1446 (2020).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Broom, A. et al. Ensemble-based enzyme design can recapitulate the effects of laboratory directed evolution in silico. Nat. Commun. 11, 4808 (2020).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Althoff, E. A. et al. Robust design and optimization of retroaldol enzymes. Protein Sci. 21, 717–726 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Giger, L. et al. Evolution of a designed retro-aldolase leads to complete active site remodeling. Nat. Chem. Biol. 9, 494–498 (2013).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Eiben, C. B. et al. Increased Diels–Alderase activity through backbone remodeling guided by Foldit players. Nat. Biotechnol. 30, 190–192 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Bjelic, S. et al. Computational design of enone-binding proteins with catalytic activity for the Morita–Baylis–Hillman reaction. ACS Chem. Biol. 8, 749–757 (2013).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Kiss, G., Rothlisberger, D., Baker, D. & Houk, K. N. Evaluation and ranking of enzyme designs. Protein Sci. 19, 1760–1773 (2010).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Frushicheva, M. P., Cao, J., Chu, Z. T. & Warshel, A. Exploring challenges in rational enzyme design by simulating the catalysis in artificial Kemp eliminase. Proc. Natl Acad. Sci. USA 107, 16869–16874 (2010).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Bunzel, H. A. et al. Evolution of dynamical networks enhances catalysis in a designer enzyme. Nat. Chem. 13, 1017–1022 (2021).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Weitzner, B. D., Kipnis, Y., Daniel, A. G., Hilvert, D. & Baker, D. A computational method for design of connected catalytic networks in proteins. Protein Sci. 28, 2036–2041 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Davey, J. A., Damry, A. M., Goto, N. K. & Chica, R. A. Rational design of proteins that exchange on functional timescales. Nat. Chem. Biol. 13, 1280–1285 (2017).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Pan, X. et al. Expanding the space of protein geometries by computational design of de novo fold families. Science 369, 1132–1136 (2021).

    ADS 
    Article 
    CAS 

    Google Scholar
     

  • Huang, P. S., Boyken, S. E. & Baker, D. The coming of age of de novo protein design. Nature 537, 320–327 (2016).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Dou, J. et al. De novo design of a fluorescence-activating β-barrel. Nature 561, 485–491 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Wei, K. Y. et al. Computational design of closely related proteins that adopt two well-defined but structurally divergent folds. Proc. Natl Acad. Sci. USA 117, 7208–7215 (2020).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Senior, A. W. et al. Improved protein structure prediction using potentials from deep learning. Nature 577, 706–710 (2020). Development of AlphaFold, a deep learning algorithm for accurate prediction of protein structure from primary sequence.

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hiranuma, N. et al. Improved protein structure refinement guided by deep learning based accuracy estimation. Nat. Commun. 12, 1340 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Baek, M. et al. Accurate prediction of protein structures and interactions using a three-track neural network. Science 373, 871–876 (2021). Development of RoseTTAFold, a freely available deep learning programme for fast and accurate prediction of protein structure.

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Anishchenko, I. et al. De novo protein design by deep network hallucination. Nature 600, 547–552 (2021).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Mazurenko, S., Prokop, Z. & Damborsky, J. Machine learning in enzyme engineering. ACS Catal. 10, 1210–1223 (2020).

    CAS 
    Article 

    Google Scholar
     

  • Ma, E. J. et al. Machine-directed evolution of an imine reductase for activity and stereoselectivity. ACS Catal. 11, 12433–12445 (2021).

    CAS 
    Article 

    Google Scholar
     

  • Bedbrook, C. N., Yang, K. K., Rice, A. J., Gradinaru, V. & Arnold, F. A. Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization. PLoS Comput. Biol. 13, e1005786 (2017).

    ADS 
    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Wu, Z., Kan, S. B. J., Lewis, R. D., Wittmann, B. J. & Arnold, F. H. Machine learning-assisted directed protein evolution with combinatorial libraries. Proc. Natl Acad. Sci. USA 116, 8852–8858 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Tischer, D. et al. Design of proteins presenting discontinuous functional sites using deep learning. Preprint at bioRxiv https://doi.org/10.1101/2020.11.29.402743.

  • Russ, W. P. et al. An evolution-based model for designing chorismate mutase enzymes. Science 369, 440–445 (2020).

    ADS 
    MathSciNet 
    CAS 
    PubMed 
    MATH 
    Article 

    Google Scholar
     

  • Wang, J. et al. Deep learning methods for designing proteins scaffolding functional sites. Preprint at bioRxiv https://doi.org/10.1101/2021.11.10.468128.

  • Hayashi, T. et al. Capture and characterization of a reactive haem–carbenoid complex in an artificial metalloenzyme. Nat. Catal. 1, 578–584 (2018).

    CAS 
    Article 

    Google Scholar
     

  • Carminati, D. M. & Fasan, R. Stereoselective cyclopropanation of electron-deficient olefins with a cofactor redesigned carbene transferase featuring radical reactivity. ACS Catal. 9, 9683–9687 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Erkkila, A., Majander, I. & Pihko, P. M. Iminium catalysis. Chem. Rev. 107, 5416–5470 (2007).

    PubMed 
    Article 
    CAS 

    Google Scholar
     

  • Mukherjee, S., Yang, J. W., Hoffmann, S. & List, B. Asymmetric enamine catalysis. Chem. Rev. 107, 5471–5569 (2007).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Doyle, A. G. & Jacobsen, E. N. Small-molecule H-bond donors in asymmetric catalysis. Chem. Rev. 107, 5713–5743 (2007).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Wurz, R. P. Chiral dialkylaminopyridine catalysts in asymmetric synthesis. Chem. Rev. 107, 5570–5595 (2007).

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Beeson, T. D., Mastracchio, A., Hong, J. B., Ashton, K. & Macmillan, D. W. Enantioselective organocatalysis using SOMO activation. Science 316, 582–585 (2007).

    ADS 
    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • St-Jacques, A. D., Eyahpaise, M.-È. C. & Chica, R. A. Computational design of multisubstrate enzyme specificity. ACS Catal. 9, 5480–5485 (2019).

    CAS 
    Article 

    Google Scholar
     

  • Davey, J. A. & Chica, R. A. Multistate approaches in computational protein design. Protein Sci. 21, 1241–1252 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     



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