Phosphoserine On Demand

By making adjustments to a quality-control factor in protein translation, researchers have genetically encoded phosphoserine into proteins (Science, DOI: 10.1126/science.1207203). Kinase enzymes make O-phosphoserine naturally, and some phosphoproteins can be synthesized. But the new development allows researchers to insert phosphoserine anywhere in a protein, extending the tool kit for studying phosphorylation. Dieter Söll and Jesse Rinehart of Yale University, Christopher J. Noren of New England Biolabs, and colleagues modified tRNA machinery from two different microbes and provided it to Escherichia coli, which is an established method for unnatural amino acid incorporation. But little O-phosphoserine was incorporated. The team surmised that the foreign tRNAs bound poorly to elongation factor-Tu (EF-Tu), a protein that shepherds tRNAs with amino acid cargo to the ribosome. The researchers in turn produced EF-Tu variants that had more productive binding to the exotic tRNA. With those modifications, they successfully used E. coli to incorporate multiple O-phosphoserine units into a human protein. They think informed tweaks to protein synthesis machinery will permit further expansion of the genetic code.