Noncanonical\nAmino Acids: Bringing New-to-Nature Functionalities\nto Biocatalysis

Biocatalysis has become an important component of modern\norganic\nchemistry, presenting an efficient and environmentally friendly approach\nto synthetic transformations. Advances in molecular biology, computational\nmodeling, and protein engineering have unlocked the full potential\nof enzymes in various industrial applications. However, the inherent\nlimitations of the natural building blocks have sparked a revolutionary\nshift. <i>In vivo</i> genetic incorporation of noncanonical\namino acids exceeds the conventional 20 amino acids, opening new avenues\nfor innovation. This review provides a comprehensive overview of applications\nof noncanonical amino acids in biocatalysis. We aim to examine the\nfield from multiple perspectives, ranging from their impact on enzymatic\nreactions to the creation of novel active sites, and subsequent catalysis\nof new-to-nature reactions. Finally, we discuss the challenges, limitations,\nand promising opportunities within this dynamic research domain.