Abstract
A dazzling array of enzymes is used by nature in making structurally complex natural products. These enzymes constitute a molecular toolbox that may be used in the construction and fine-tuning of pharmaceutically active molecules. Aided by technological advancements in protein engineering, it is now possible to tailor the activities and specificities of these enzymes as biocatalysts in the production of both natural products and their unnatural derivatives. These efforts are crucial in drug discovery and development, where there is a continuous quest for more potent agents. Both rational and random evolution techniques have been utilized in engineering these enzymes. This review will highlight some examples from several large families of natural products.
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Due to space constraints, we apologize for any work that we were not able to cite. Related projects in our laboratory are supported by the NIH, David and Lucile Packard, Alfred Sloan and Dreyfus Foundations. R. Cacho and A. Zabala are supported by the NIH predoctoral training grants.
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Angelica O. Zabala and Ralph A. Cacho contributed equally to this work.
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Zabala, A.O., Cacho, R.A. & Tang, Y. Protein engineering towards natural product synthesis and diversification. J Ind Microbiol Biotechnol 39, 227–241 (2012). https://doi.org/10.1007/s10295-011-1044-2
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DOI: https://doi.org/10.1007/s10295-011-1044-2