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The process of natural evolution as given rise to the amazing variety of proteins observed in natura, and yet for every known protein amino acid sequence there is an unknown number of sequences as yet undiscovered. Understanding how evolution has generated this diversity provides can guide the design of proteins with novel properties. A brief outline of some of the processes observed in natural evolution, such as random mutation and domain shuffling, will be linked to examples of protein design which use these natural design principles with emphasis on the design of novel biocatalysts. Where relevant, biophysical characterization of the designed proteins can provide valuable and unexpected insights as to their function. This work was supported by Conselho Nac. Des. Cient. Tecnologico (CNPq 310840/2021-0 and 465319/2014-9) and FAPESP (2014/50884-5)
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