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Combinatorial and computational challenges for biocatalyst design

Abstract

Nature provides a fantastic array of catalysts extremely well suited to supporting life, but usually not so well suited for technology. Whether biocatalysis will have a significant technological impact depends on our finding robust routes for tailoring nature's catalysts or redesigning them anew. Laboratory evolution methods are now used widely to fine-tune the selectivity and activity of enzymes. The current rapid development of these combinatorial methods promises solutions to more complex problems, including the creation of new biosynthetic pathways. Computational methods are also developing quickly. The marriage of these approaches will allow us to generate the efficient, effective catalysts needed by the pharmaceutical, food and chemicals industries and should open up new opportunities for producing energy and chemicals from renewable resources.

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Figure 1: Catalytic plasticity in a family of fatty-acid synthesis enzymes.
Figure 2: Molecular breeding by DNA shuffling.
Figure 3: Evolution of pathways that synthesize carotenoid pigments.

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Acknowledgements

I thank the many talented students and postdocs who have contributed to the development of new biocatalyst engineering tools in my laboratory, and the following organizations for their financial support: the US Office of Naval Research, the US National Science Foundation, the Army Research Office, Maxygen, Inc., The Biotechnology Research & Development Corporation, British Petroleum, Degussa AG and Procter & Gamble Co. I also thank C. Voigt and J. Shanklin for thoughtful comments, and J. Shanklin for Fig. 1.

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Arnold, F. Combinatorial and computational challenges for biocatalyst design. Nature 409, 253–257 (2001). https://doi.org/10.1038/35051731

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