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2.3.3.3.3 Polyketide Synthases

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Antibiotics such as erythromycin are made by large multidomain proteins called polyketide synthases. Site-directed mutagenesis was used to modify the substrate specificity of one polyketide synthase reaction so that the product contains a malonate unit, whereas the product of the original enzyme contained a methylmalonate unit. In addition to site-directed mutagenesis, the order of the polyketide synthase domains was shuffled to create proteins that could catalyze the synthesis of new antibiotics. An extension of site-directed mutagenesis allows non-natural amino acids to be incorporated into proteins. Non-natural amino acids are not naturally encoded by the genome, but instead include a wide variety of amino acids that are present in cells or produced by synthetic methods [117].

Biomolecules from Natural Sources

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