Journal
CHEMBIOCHEM
Volume 20, Issue 11, Pages 1357-1364Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201800733
Keywords
cyclic peptides; genetic code expansion; protein engineering; synthetic biology; unnatural amino acids
Funding
- Netherlands Organisation for Scientific Research (NWO, Veni grant) [722.017.007]
- Marie Sklodowska Curie Individual Fellowship [751509]
- Marie Curie Actions (MSCA) [751509] Funding Source: Marie Curie Actions (MSCA)
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Expanding the genetic code of organisms by incorporating noncanonical amino acids (ncAAs) into target proteins through the suppression of stop codons in vivo has profoundly impacted how we perform protein modification or detect proteins and their interaction partners in their native environment. Yet, with genetic code expansion strategies maturing over the past 15 years, new applications that make use-or indeed repurpose-these techniques are beginning to emerge. This Concept article highlights three of these developments: 1) The incorporation of ncAAs for the biosynthesis and selection of bioactive macrocyclic peptides with novel ring architectures, 2) synthetic biocontainment strategies based on the addiction of microorganisms to ncAAs, and 3) enzyme design strategies, in which ncAAs with unique functionalities enable the catalysis of new-to-nature reactions. Key advances in all three areas are presented and potential future applications discussed.
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