On Jun 7th, 2024, Shixian Lin’s Lab from Life Sciences Institute, Zhejiang University, published a research article in Science entitled “Rare codon recoding for efficient noncanonical amino acid incorporation in mammalian cells”.

The ability to genetically encode noncanonical amino acids (ncAAs) has empowered proteins with improved or previously unknown properties. However, existing strategies in mammalian cells rely on the introduction of a blank codon to incorporate ncAAs, which is inefficient and limits their widespread applications. In this study, the authors developed a rare codon recoding strategy that takes advantage of the relative rarity of the TCG codon to achieve highly selective and efficient ncAA incorporation through systematic engineering and big data–model predictions. They highlight the broad utility of this strategy for the incorporation of dozens of ncAAs into various functional proteins at the wild-type protein expression levels, as well as the synthesis of proteins with up to six-site ncAAs or four distinct ncAAs in mammalian cells for downstream applications.

Figure 1. Schematic of rare codon recoding for ncAA incorporation.

Dr. Wenlong Ding, Wei Yu and Dr. Yulin Chen are the co-first authors and Dr. Shixian Lin is the corresponding author in this study. This research was supported by the Ministry of Science and Technology of China, the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China, China Postdoctoral Science Foundation, the Postdoctoral Fellowship Program of CPSF, the State Key Laboratory of Transvascular Implantation Devices, and the Feng Foundation of Biomedical Research.

Link: https://www.science.org/doi/10.1126/science.adm8143