Chapter 5: In vitro synthetic biology of the genetic code: its development and applications
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Published:02 Jun 2014
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H. Suga, C. John Hipolito, Y. Goto, T. Katoh, and N. Kato Bashiruddin, in Synthetic Biology, Volume 1, ed. M. Ryadnov, L. Brunsveld, and H. Suga, The Royal Society of Chemistry, 2014, vol. 1, ch. 5, pp. 126-163.
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Ribosomal synthesis is governed by the genetic code, consisting of 64 codons that assign 20 proteinogenic amino acids as well as initiation and termination. Despite the fact that this biosynthetic process generally synthesizes large proteins, nature has evolved other processes for the synthesis of short peptides, involving post-translational modification enzymes or even alternative machinery, so-called non-ribosomal peptide synthetases. These nonstandard peptides often bear unique structural features, such as nonproteinogenic amino acid sidechains, backbone modification, and macrocyclic structure, which grant them enhanced structural rigidity, protease resistance and membrane penetration. Unfortunately, it is yet a demanding challenge for researchers to biosynthesize completely de novo peptide molecules by means of these systems. On the other hand, inspired by these nonstandard peptides bearing nonproteinogenic elements, some researchers have used combinations of chemical and biological techniques to expand or reprogram the genetic code to accommodate nonproteinogenic amino acids containing chemical building blocks, and have achieved ribosomal synthesis of nonstandard peptides. In a new light cast by in vitro synthetic biology, development of these artificial genetic codes, the scope and limitations of presently available technologies, including mRNA template-directed production and selection of bioactive nonstandard peptides, will be presented in this chapter.