Upgrading Protein Synthesis for Synthetic Biology — ASN Events
  1. Schedule
  2. Session 1: Synthetic and Chemical Biology
  3. Upgrading Protein Synthesis for Synthetic Biology

Upgrading Protein Synthesis for Synthetic Biology (#3)

Dieter Söll 1
  1. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States

At the time of its elucidation the genetic code was suggested to be universal in all organ­isms, and the result of a ‘frozen accident’ unable to evolve further (1). Today we know 22 natural amino acids (2): selenocysteine, the 21st, and pyrrolysine, the 22nd, are di­rectly inserted into growing polypeptides during translation. The incorporation of seleno­cysteine directed by UGA requires the action of specific RNA and protein elements. In contrast, pyrrolysine is ligated directly to a suppressor tRNAPyl and inserted into proteins in response to UAG codons. Based on the realization that protein plasticity is a feature of living cells (3), man-made expan­sion of the genetic code based on orthogonal translation systems (OTSs) is an active research field (4). However, the successful design of in vivo active and specific OTS systems is far from ideal (5). This will be illustrated at the examples of co-translational insertion of O-phosphoserine (6,7) and selenocysteine (8,9). 

  1. Crick (1968) The origin of the genetic code. J Mol Biol 38, 367.
  2. Ambrogelly et al (2007) Natural expansion of the genetic code. Nat Chem Biol 3, 29.
  3. Ruan et al (2008) Qual¬ity control despite mistranslation caused by an ambiguous genetic code. Proc Natl Acad Sci USA 105, 16502.
  4. Liu, Schultz (2010) Adding new chemistries to the genetic code. Annu Rev Biochem 79, 413.
  5. O’Donoghue et al (2013) Upgrading protein synthesis for synthetic biology. Nat Chem Biol 9, 594.
  6. Park et al (2011) Expanding the genetic code of Escherichia coli with phosphoserine. Science 333, 1151.
  7. Lee et al (2013) A facile strategy for selective phosphoserine incorporation in histones. Angew Chem Int Ed Engl 52, 5771
  8. Aldag et al (2013) Rewiring translation for elongation factor Tu-dependent selenocysteine incorporation. Angew Chem Int Ed Engl 52, 1441.
  9. Bröcker et al (2013) Recoding the genetic code with selenocysteine. Angew Chem Int Ed Engl, doi 10.1002/anie.201308584.