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Featured Event

11/5 - Seminar (chemical biology): Wenshe Liu Texas A&M University

Wenshe Liu - Liu Group website
Department of Chemistry
Texas A&M University
Host: Haw Yang

Pyrrolysyl-tRNA synthetase: a mediocre enzyme could be a gift from nature

Pyrrolysine is the natural existing 22nd proteinogenic amino acid. Its genetic incorporation is achieved through the engagement of a stop codon and a unique pyrrolysyl-tRNA synthetase-tRNA pair. By engineering the pyrrolysine translational machinery, we have shown that a large variety of noncanonical amino acids can be genetically incorporated into proteins in E. coli. This has allowed the synthesis of proteins such as histones with posttranslational lysine acetylation and methylation and labeling proteins with different biophysical and biochemical probes for their functional analysis. We have also showed that the pyrrolysine translational machinery can be coupled together with an evolved tyrosine translational machinery to genetically incorporate two different noncanonical amino acids into one protein in E. coli. This achievement opens the gate for the synthesis of a protein with two different posttranslational modifications and the construction of phage displayed peptide libraries that comprise 22 different amino acid building blocks.

References

1. Wang Y.-S., Fang X., Wallace A.L., Wu B. & Liu W.R.*, “A Rationally Designed Pyrrolysyl-tRNA Synthetase Mutant Has a Broad Substrate Specificity”, J. Am. Chem. Soc., 2012, 134, 2950-2953.

2. Wang Y.-S., Russell W.K., Wang Z., Wan W., Dodd L.E., Pai P.-J., Russell D.H., & Liu W.R.*, “The De Novo Engineering of Pyrrolysyl-tRNA Synthetase for Genetic Incorporation of L-phenylalanine and Its Derivatives”, Mol. BioSyst., 2011, 7: 714-717.

3. Wang Y.-S., Wu B., Wang Z., Huang Y., Wan W., Russell W.K., Pai P.-J., Russell D.H. & Liu W.R.*, “Genetic Incorporation of A Photocaged Ne-methyl-L-lysine into Proteins” Mol. Biosyst., 2010, 6: 1557-1560.

4. Wan W., Huang Y., Wang Z., Russell W.K., Pai P.-J., Russell D.H. & Liu W.R.*, “A Facile System for Genetic Incorporation of Two Different Noncanonical Amino Acids into One Protein in Escherichia coli”, Angew. Chem. Int. Ed., 2010, 3211-3214.

5. Huang Y., Russell W.K., Wan W., Pai P.-J., Russell D.H. & Liu W.*, “A convenient Method for Genetic Incorporation of Multiple Noncanonical Amino Acids into One Protein in Escherichia coli”. Mol. BioSyst. 2010, 6, 683-686.