Directed enzyme evolution: beyond the low-hanging fruit

Current Opinion in Structural Biology
Moshe Goldsmith, Dan S Tawfik

Abstract

The field of directed evolution has progressed to the point where it is feasible to engineer enzymes for unnatural substrates and reactions with catalytic efficiencies and regio-specificity or stereo-specificity that rival those of natural enzymes. Here, we describe the conceptual and methodological advances that have enabled this progress. We address methodologies based on small libraries enriched with improved variants and carrying compensatory stabilizing mutations. Such libraries can be combined with low-throughput screens that provide high accuracy and directly target the desired substrate and reaction conditions, and thereby provide highly improved variants.

References

Jul 24, 2003·Protein Science : a Publication of the Protein Society·Michelle M MeyerFrances H Arnold
Aug 29, 2006·Current Opinion in Chemical Biology·Margaret E GlasnerPatricia C Babbitt
Dec 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thomas P TreynorStephen L Mayo
May 8, 2007·Protein Engineering, Design & Selection : PEDS·Asael Herman, Dan S Tawfik
Dec 1, 2007·Nature Methods·Sergio G Peisajovich, Dan S Tawfik
May 23, 2008·Journal of Molecular Biology·Shimon BershteinDan S Tawfik
Jul 16, 2008·Journal of Molecular Biology·Rudi FasanFrances H Arnold
Aug 21, 2008·Chembiochem : a European Journal of Chemical Biology·Manfred T Reetz, Joaquin Sanchis
Oct 22, 2008·Nature Methods·Rinkoo D Gupta, Dan S Tawfik
Nov 18, 2008·Applied and Environmental Microbiology·Daniel J KochFrances H Arnold
Jan 24, 2009·Protein Science : a Publication of the Protein Society·Yong ChenZhanglin Lin
May 26, 2009·Nucleic Acids Research·Antonin PavelkaJiri Damborsky
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Paul M MurphyDavid Baker
May 30, 2009·Nature Protocols·Navin VaradarajanBrent L Iverson
Aug 4, 2009·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Wei ZhengChris Bailey-Kellogg
Sep 22, 2009·Current Opinion in Structural Biology·Nobuhiko Tokuriki, Dan S Tawfik
Oct 6, 2009·Journal of the American Chemical Society·Jung-uk ShimFlorian Hollfelder
Nov 21, 2009·Journal of the American Chemical Society·Navin VaradarajanBrent L Iverson
Nov 26, 2009·Nature Reviews. Molecular Cell Biology·Philip A Romero, Frances H Arnold
Dec 18, 2009·Proteins·James T MacDonaldWilliam R Taylor
Dec 29, 2009·Journal of Molecular Biology·Olga KhersonskyDan S Tawfik
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Fei ChenSteven A Benner
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sheng WuManfred T Reetz
Feb 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jeremy J AgrestiDavid A Weitz
Feb 23, 2010·Current Opinion in Microbiology·Dominique Böttcher, Uwe T Bornscheuer
Mar 6, 2010·Current Protein & Peptide Science·Nikolaos E Labrou
Mar 27, 2010·Chemistry & Biology·Lucia GranieriChristoph A Merten
Apr 10, 2010·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Wei ZhengChris Bailey-Kellogg
May 21, 2010·Trends in Biotechnology·Misha V Golynskiy, Burckhard Seelig
Jul 8, 2010·ACS Chemical Biology·Thomas C ScanlonKarl E Griswold
Jul 17, 2010·Nature Reviews. Genetics·Misha Soskine, Dan S Tawfik
Aug 4, 2010·Chembiochem : a European Journal of Chemical Biology·Helge Jochens, Uwe T Bornscheuer
Aug 17, 2010·Applied and Environmental Microbiology·Moran BroukAyelet Fishman
Aug 19, 2010·Protein Science : a Publication of the Protein Society·David Baker
Sep 21, 2010·Current Opinion in Biotechnology·Christian Jäckel, Donald Hilvert
Sep 28, 2010·Current Opinion in Biotechnology·Stefan Lutz
Sep 28, 2010·Current Opinion in Chemical Biology·Balint KintsesFlorian Hollfelder

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Citations

May 3, 2014·Journal of Biotechnology·Carlos G Acevedo-RochaManfred T Reetz
Oct 14, 2014·Current Opinion in Chemical Biology·Michael D Lane, Burckhard Seelig
Dec 4, 2012·International Journal of Molecular Sciences·Alexandre BarrozoShina Caroline Lynn Kamerlin
Jan 30, 2016·Journal of the American Chemical Society·Karin M KroneDetlev Belder
Jan 17, 2016·Current Opinion in Structural Biology·Sankaran SandhyaNarayanaswamy Srinivasan
Nov 5, 2015·Molecular Biology and Evolution·Marisa L Winkler, Robert A Bonomo
Apr 23, 2013·Current Opinion in Structural Biology·Darren J Hart, Geoffrey S Waldo
Oct 30, 2012·Current Opinion in Biotechnology·Arren Bar-Even, Dan Salah Tawfik
Nov 26, 2015·Journal of Industrial Microbiology & Biotechnology·Youran LiGuiyang Shi
Dec 30, 2015·Applied Biochemistry and Biotechnology·Hui LuoZhongyao Shen
Jul 28, 2016·Technology·Justin R Klesmith, Timothy A Whitehead
Jun 21, 2015·Current Opinion in Structural Biology·Derek N WoolfsonChristopher W Wood
Jun 21, 2015·Current Opinion in Structural Biology·Igor DodevskiCasim A Sarkar
May 8, 2013·The FEBS Journal·Hein J Wijma, Dick B Janssen
Apr 13, 2013·The FEBS Journal·Teunke van RossumJohn van der Oost
Mar 29, 2014·Biotechnology Journal·Agata StaniekHeribert Warzecha
Apr 6, 2016·Journal of Biotechnology·Anita Emmerstorfer-AugustinHarald Pichler
Sep 1, 2015·Nature Chemical Biology·Shun-Ichi TanakaShohei Koide
Jul 31, 2013·Current Opinion in Structural Biology·Xiuwei ZhangSarah A Teichmann
Jun 20, 2015·Trends in Biotechnology·Yuvaraj RavikumarHyungdon Yun
Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Donald R OrtXin Guang Zhu
Jul 12, 2012·Journal of Biotechnology·Giulia GonnelliYves Dehouck
May 2, 2016·Current Opinion in Biotechnology·Anthony BurgardHarry Yim
Apr 27, 2016·Biomacromolecules·Jason S KahnDan Luo
Sep 24, 2015·PLoS Computational Biology·Noah OllikainenTanja Kortemme
Jan 30, 2016·Protein Science : a Publication of the Protein Society·Olga Khersonsky, Sarel J Fleishman
Jul 15, 2016·Biophysical Journal·Liskin Swint-Kruse
Aug 16, 2016·Journal of Industrial Microbiology & Biotechnology·Jorick FranceusTom Desmet
Apr 11, 2017·Microbial Biotechnology·Teunke van RossumServé W M Kengen
Feb 26, 2016·Chemistry : a European Journal·Zhoutong SunManfred T Reetz
Jun 16, 2015·Industrial & Engineering Chemistry Research·Han XiaoHuimin Zhao
Oct 22, 2015·Chembiochem : a European Journal of Chemical Biology·Cindy WechslerKai Tittmann

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