Genome recoding strategies to improve cellular properties: mechanisms and advances
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aBIOTECH
REVIEW
Genome recoding strategies to improve cellular properties: mechanisms and advances Tanya Singh1 , Sudesh Kumar Yadav2 , Alexander Vainstein3 , Vinay Kumar1& 1 2 3
Department of Botany, School of Basic Sciences, Central University of Punjab, Bathinda 151001, India Center of Innovative and Applied Biotechnology, Mohali 140306, India Institute of Plant Sciences and Genetics in Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel
Received: 3 March 2020 / Accepted: 7 October 2020
Abstract
The genetic code, once believed to be universal and immutable, is now known to contain many variations and is not quite universal. The basis for genome recoding strategy is genetic code variation that can be harnessed to improve cellular properties. Thus, genome recoding is a promising strategy for the enhancement of genome flexibility, allowing for novel functions that are not commonly documented in the organism in its natural environment. Here, the basic concept of genetic code and associated mechanisms for the generation of genetic codon variants, including biased codon usage, codon reassignment, and ambiguous decoding, are extensively discussed. Knowledge of the concept of natural genetic code expansion is also detailed. The generation of recoded organisms and associated mechanisms with basic targeting components, including aminoacyl-tRNA synthetase–tRNA pairs, elongation factor EF-Tu and ribosomes, are highlighted for a comprehensive understanding of this concept. The research associated with the generation of diverse recoded organisms is also discussed. The success of genome recoding in diverse multicellular organisms offers a platform for expanding protein chemistry at the biochemical level with non-canonical amino acids, genetically isolating the synthetic organisms from the natural ones, and fighting viruses, including SARS-CoV2, through the creation of attenuated viruses. In conclusion, genome recoding can offer diverse applications for improving cellular properties in the genome-recoded organisms.
Keywords Genetic code, Codon usage, Protein engineering, Attenuated virus
INTRODUCTION The initial concept of a universal genetic code now has many exceptions. The investigation of translation machinery, as well as sequencing, has provided many examples of genetic code variations; in fact, these are routinely observed in numerous organisms, including fungi, bacteria, archaea, and viruses (Ambrogelly et al. 2007). Although genetic code variation has been observed under natural conditions, it is often restricted to the stop codon. The first report on the redefinition of & Correspondence: [email protected] (V. Kumar)
a stop codon, UGA, was in RNA phage Qb (Weiner and Weber 1971). Selenocysteine (Sec), a noncoding amino acid, was also documented to be encoded by the stop codon UGA in 1986. Collectively, these variations from the standard genetic code were initially documented as deleterious. However later, this mechanism was determined to be widespread in nature and to impart microbial fitness under sp
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