Abstract:
:Several significant steps have been completed toward a general method for the site-specific incorporation of unnatural amino acids into proteins in vivo. An "orthogonal" suppressor tRNA was derived from Saccharomyces cerevisiae tRNA2Gln. This yeast orthogonal tRNA is not a substrate in vitro or in vivo for any Escherichia coli aminoacyl-tRNA synthetase, including E. coli glutaminyl-tRNA synthetase (GlnRS), yet functions with the E. coli translational machinery. Importantly, S. cerevisiae GlnRS aminoacylates the yeast orthogonal tRNA in vitro and in E. coli, but does not charge E. coli tRNAGln. This yeast-derived suppressor tRNA together with yeast GlnRS thus represents a completely orthogonal tRNA/synthetase pair in E. coli suitable for the delivery of unnatural amino acids into proteins in vivo. A general method was developed to select for mutant aminoacyl-tRNA synthetases capable of charging any ribosomally accepted molecule onto an orthogonal suppressor tRNA. Finally, a rapid nonradioactive screen for unnatural amino acid uptake was developed and applied to a collection of 138 amino acids. The majority of glutamine and glutamic acid analogs under examination were found to be uptaken by E. coli. Implications of these results are discussed.
journal_name
Proc Natl Acad Sci U S Aauthors
Liu DR,Schultz PGdoi
10.1073/pnas.96.9.4780keywords:
subject
Has Abstractpub_date
1999-04-27 00:00:00pages
4780-5issue
9eissn
0027-8424issn
1091-6490journal_volume
96pub_type
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