Efforts and Challenges in Engineering the Genetic Code.
This year marks the 48th anniversary of Francis Crick's seminal work on the origin of the genetic code, in which he first proposed the "frozen accident" hypothesis to describe evolutionary selection against changes to the genetic code that cause devastating global proteome modification. However, numerous efforts have demonstrated the viability of both natural and artificial genetic code variations. Recent advances in genetic engineering allow the creation of synthetic organisms that incorporate noncanonical, or even unnatural, amino acids into the proteome. Currently, successful genetic code engineering is mainly achieved by creating orthogonal aminoacyl-tRNA/synthetase pairs to repurpose stop and rare codons or to induce quadruplet codons. In this review, we summarize the current progress in genetic code engineering and discuss the challenges, current understanding, and future perspectives regarding genetic code modification.
School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong, China. xlin@link.cuhk.edu.hk.
Xiao
X
Lin
School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong, China. allenyu@cuhk.edu.hk.
Allen Chi Shing
AC
Yu
School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong, China. tf.chan@cuhk.edu.hk.
Ting Fung
TF
Chan
evolution; frozen accident; genetic code; genetic engineering; synthetic biology