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Engineering the third wave of biocatalysis

Nature volume 485, pages 185–194 (2012)Cite this article

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Abstract

Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.

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Figure 1: The evolution of enzyme discovery and protein engineering strategies used to identify desired catalysts.
Figure 2: Free energy (Δ G ) connects design goals to the required structural changes via protein engineering strategies.
Figure 3: Different enzymatic routes to the synthesis of the key side chain of atorvastatin (Lipitor).
Figure 4: Biocatalysis advances synthetic chemistry.

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Acknowledgements

We thank H.-P. Meyer and R. Fox for discussions. R.J.K. thanks the US National Science Foundation (CBET-0932762) and the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (WCU programme R32-2008-000-10213-0). U.T.B. and S.L. thank the German Research Foundation (SPP 1170, Bo1864/4-1) and, respectively, the US National Science Foundation (CBET-0730312) for financial support.

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Authors and Affiliations

  1. Department of Biotechnology & Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Felix-Hausdorff-Straße 4, D-17487 Greifswald, Germany,

    U. T. Bornscheuer

  2. Codexis Inc., 200 Penobscot Drive, Redwood City, California, 94063, USA

    G. W. Huisman

  3. Department of Biochemistry, Molecular Biology and Biophysics, Biotechnology Institute, University of Minnesota, 1479 Gortner Avenue, Saint Paul, Minnesota 55108, USA,

    R. J. Kazlauskas

  4. Department of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea,

    R. J. Kazlauskas

  5. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, USA,

    S. Lutz

  6. Merck Research Laboratories, Merck & Co., Rahway, New Jersey, 07065, USA

    J. C. Moore

  7. Lonza AG, Valais Works, CH-3930 Visp, Switzerland,

    K. Robins

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Contributions

U.T.B., R.J.K. and S.L. drafted the text; K.R., G.W.H. and J.C.M. collected the examples for industrial applications; and the authors together wrote and edited the review. All authors contributed equally.

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Correspondence to U. T. Bornscheuer.

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Competing interests

K.R. is an employee of Lonza AG, G.W.H. is an employee of Codexis Inc. and J.C.M. is an employee of Merck & Co. Inc. All three companies are working on biocatalysis.

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Bornscheuer, U., Huisman, G., Kazlauskas, R. et al. Engineering the third wave of biocatalysis. Nature 485, 185–194 (2012). https://doi.org/10.1038/nature11117

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