Rewiring protein synthesis: From natural to synthetic amino acids

• Published in: Biochimica et biophysica acta Vol. 1861; no. 11; pp. 3024 - 3029
• Main Authors: Fan, Yongqiang, Evans, Christopher R., Ling, Jiqiang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2017
• Subjects: amino acids; Amino Acids - chemical synthesis; Amino Acids - metabolism; aminoacyl tRNA ligases; Animals; Cloning, Molecular - methods; Codon - chemical synthesis; Codon - chemistry; Codon - metabolism; codons; evolution; genetic code; Genetic Code - physiology; Humans; messenger RNA; Models, Molecular; Protein Biosynthesis - physiology; Protein Engineering - methods; protein synthesis; quality control; ribosomes; synthetic biology; Synthetic Biology - methods; translation (genetics)
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/j.bbagen.2017.01.014

The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome. We will discuss evolution and engineering of such components that allow incorporation of natural and synthetic amino acids at positions that deviate from the standard genetic code. The protein synthesis machinery is highly selective, yet not fixed, for the correct amino acids that match the mRNA codons. Ambiguous translation of a codon with multiple amino acids or complete reassignment of a codon with a synthetic amino acid diversifies the proteome. Expanding the genetic code with synthetic amino acids through rewiring protein synthesis has broad applications in synthetic biology and chemical biology. Biochemical, structural, and genetic studies of the translational quality control mechanisms are not only crucial to understand the physiological role of translational fidelity and evolution of the genetic code, but also enable us to better design biological parts to expand the proteomes of synthetic organisms. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O’Donoghue. •The protein synthesis machinery is selective for natural amino acid substrates.•Translational fidelity can be compromised under stress conditions.•Engineering of aaRSs, EF-Tu, and the ribosome expands the genetic code.