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Enzyme evolution

Design by necessity

Nature volume 403, pages 606–607 (2000)Cite this article

”The designs of his bright imagination were never etched by the sharp fumes of necessity”, commented the English poet Francis Thompson in the Dublin Review of 1908. The poetry of Percy Bysshe Shelley may indeed, as Thompson concluded, have been designed in the fire of his imagination. Protein structure, on the other hand, is etched entirely by the sharp fumes of necessity, through the process of natural selection. On page 617 of this issue, Altamirano et al.1 show that a combination of design and necessity can rapidly evolve one enzyme in a biosynthetic pathway into another. As well as providing a possible model for the natural evolution of new enzyme activities from an existing scaffold, the success of this procedure suggests that the particular scaffold they use may have advantages in the directed evolution of new biocatalysts.

The first efforts to design proteins de novo aimed to create sequences, which adopt a particular fold that is stable at ordinary temperatures2,3. Parallel efforts to engineer new functions into natural proteins began by altering specificity using site-directed mutagenesis4. Despite some success with both, the creation of totally new enzyme activity by either of these ‘rational’ approaches has proven to be extremely difficult. No surprise, then, that the latest attempts have borrowed a leaf or two from nature's book.

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Figure 1: The folded polypeptide chain of triosephosphate isomerase, the archetypal TIM-barrel enzyme.

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  1. Rosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South Street, Waltham, 02454-9110, Massachusetts, USA

    Gregory A. Petsko

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  1. Gregory A. Petsko
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Correspondence to Gregory A. Petsko.

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Petsko, G. Design by necessity. Nature 403, 606–607 (2000). https://doi.org/10.1038/35001176

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