Nature Biotechnology
- 24, 1436 - 1440 (2006)
Published online: 29 October 2006; | doi:10.1038/nbt1254
Recombinant expression of selectively sulfated proteins in Escherichia coliChang C Liu1 & Peter G Schultz1, 21
Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. 2
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
Correspondence should be addressed to Peter G Schultz schultz@scripps.edu or Chang C Liu ccliu@scripps.edu Although tyrosine sulfation is a post-translational modification widespread across multicellular eukaryotes1, its biological functions remain largely unknown. This is in part due to the difficulties of synthesizing selectively sulfated proteins. Here we report the selective incorporation of sulfotyrosine into proteins in bacteria by genetically encoding the modified amino acid in response to the amber nonsense codon TAG. Moreover, we show that this strategy enables direct expression in Escherichia coli of sulfo-hirudin, previously inaccessible through recombinant methods. The affinity of sulfo-hirudin toward human thrombin is enhanced more than tenfold over that of desulfo-hirudin, suggesting that sulfo-hirudin may offer clinical advantages for use as an anticoagulant2. This general approach to the biosynthesis of sulfated proteins should facilitate further study and application of tyrosine sulfation.
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