Engineering of artificial metalloproteins is an expanding field with potential impacts in many areas from fundamental understanding of protein structure and function to industrial production of specialty chemicals such as chiral drug intermediates. Incorporation of unnatural amino acids and non‐native metal cofactors into proteins is an emerging field in the area of protein design, as it offers the tantalizing prospect of introducing new functionality and provides exquisite probes for and fine‐tuning of native protein properties. Although it is a relatively young field, engineering of non‐native metalloproteins boasts a myriad of techniques for design, construction, and/or expression of the desired artificial protein. Additionally, many groundbreaking studies exist in this field that have enhanced basic scientific understanding of protein function or generated promising artificial enzymes. Discussion of the techniques prominent for incorporation of unnatural amino acids and non‐native cofactors is followed by some of the most interesting applications of these techniques reported to date.
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