When protein engineering confronts the tRNA world.

Abstract

A long-outstanding goal of protein engineering has run up against the tRNA world, a situation that, in turn, makes the achievement of that goal a formidable challenge. The goal is to expand the genetic code to allow for incorporation of additional, nonnatural, amino acids at predetermined sites in proteins that are synthesized in vivo. Achieving this goal would enable a variety of applications, including structure–function analysis of specific sites in proteins by means of probes inserted at defined locations and the creation of proteins with new chemical activities. With protein-based therapeutics now realized with examples such as erythropoietin, growth hormone, and α-interferon, among others, the possibility of therapeutic proteins with novel chemical or biological substituents can also be taken seriously. But to synthesize such proteins requires a major intrusion into the tRNA world and some of the complexities that it contains. A paper by Liu et al. (1) in this issue illustrates the point.