Incorporation of non-natural modules into proteins: structural features beyond the genetic code

Abstract

The biotechnological application of enzymes necessitates a permanent quest for new biocatalysts. Among others, improvement of catalytic activity, modification of substrate specificity, or increase in stability of the enzymes are desirable goals. The exploration of homologous enzymes from various sources or DNA-based methods, like site-directed mutagenesis or directed evolution, yield an incredible variety of biocatalysts but they all rely on the restricted number of canonical amino acids. Chemistry offers an almost unlimited palette of additional modifications which can endow the proteins with improved or even completely new properties. Numerous techniques to furnish proteins with non-natural amino acids or non-proteinogenic modules have been introduced and are reviewed with special focus on expressed protein ligation, a method that combines the potential of protein biosynthesis and chemical synthesis.