Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Feb;13(1):10-8.
doi: 10.1016/j.cbpa.2009.01.014. Epub 2009 Feb 23.

Enzyme (re)design: lessons from natural evolution and computation

John A Gerlt  1 , Patricia C Babbitt
Affiliations
Review

Enzyme (re)design: lessons from natural evolution and computation

John A Gerlt et al. Curr Opin Chem Biol. 2009 Feb.

Abstract

The (re)design of enzymes to catalyze 'new' reactions is a topic of considerable practical and intellectual interest. Directed evolution (random mutagenesis followed by screening/selection) has been used widely to identify novel biocatalysts. However, 'rational' approaches using either natural divergent evolution or computational predictions based on chemical principles have been less successful. This review summarizes recent progress in evolution-based and computation-based (re)design.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Progenitors, (re)designed reactions, and kinetic constants for the “new” reactions obtained using evolution-based approaches.
Figure 2
Figure 2
Progenitors, (re)designed reactions, and kinetic constants for enhanced promiscuous reactions obtained using evolution-based approaches.
Figure 3
Figure 3
Progenitor, (re)designed reaction, and kinetic constants for a “new” reaction obtained using evolution-based grafting of loops.
Figure 4
Figure 4
Progenitors, (re)designed reactions, and kinetic constants for “new” reactions obtained using computation-based approaches.
See this image and copyright information in PMC

Comment in

  • Engineering enzymes by 'intelligent' design.
    Kazlauskas R, Lutz S. Kazlauskas R, et al. Curr Opin Chem Biol. 2009 Feb;13(1):1-2. doi: 10.1016/j.cbpa.2009.02.022. Epub 2009 Mar 9. Curr Opin Chem Biol. 2009. PMID: 19272831 Free PMC article. No abstract available.

References

    1. Nixon AE, Firestine SM, Salinas FG, Benkovic SJ. Rational design of a scytalone dehydratase-like enzyme using a structurally homologous protein scaffold. Proc Natl Acad Sci U S A. 1999;96:3568–3571. - PMC - PubMed
    1. Jurgens C, Strom A, Wegener D, Hettwer S, Wilmanns M, Sterner R. Directed evolution of a (beta alpha)8-barrel enzyme to catalyze related reactions in two different metabolic pathways. Proc Natl Acad Sci U S A. 2000;97:9925–9930. - PMC - PubMed
    1. Seebeck FP, Hilvert D. Conversion of a PLP-dependent racemase into an aldolase by a single active site mutation. J Am Chem Soc. 2003;125:10158–10159. - PubMed
    1. Hederos S, Broo KS, Jakobsson E, Kleywegt GJ, Mannervik B, Baltzer L. Incorporation of a single His residue by rational design enables thiol-ester hydrolysis by human glutathione transferase A1-1. Proc Natl Acad Sci U S A. 2004;101:13163–13167. - PMC - PubMed
    1. Woycechowsky KJ, Vamvaca K, Hilvert D. Novel enzymes through design and evolution. Adv Enzymol Relat Areas Mol Biol. 2007;75:241–294. xiii. - PubMed

Publication types

LinkOut - more resources