title: Congeneric bio-adhesive mussel foot proteins designed by modified prolines revealed a chiral bias in unnatural translation.
abstract: Chiral bias in the unnatural translation and 'sticky' mussel proteins. The residue-specific in vivo incorporation of hydroxylated amino acids as well as other synthetic analogs, such as fluoroprolines, emerges as the method of choice for recombinant synthesis of Pro-rich mussel adhesive protein congeners. Chemical diversifications introduced in this way provide a general route towards bio-adhesive congeners endowed with properties not developed by natural evolution. Most importantly, we have found that the co-translational incorporation of (4R)-, and (4S)-hyroxylated and fluorinated analogs into mussel proteins presented a chiral bias: the expressed protein was only detectable in samples incubated with analogs with (4R)-substituents. Possible relationship of these stereochemical preferences for (4R)-stereoisomers in the translation to intracellular tRNA concentrations, ribosomal editing and proofreading or structural effects such as preorganization remains to be addressed in future studies. These studies will generally provide a mechanistic framework for the flexibility of the translational machinery and establish the boundaries of the unnatural translation.
authors.affiliation: Department of Chemistry, Biocatalysis Group, Berlin Institute of Technology/TU Berlin, Franklinstraße 29, D-10587 Berlin, Germany.
authors.forename: Maud
authors.initials: M
authors.lastname: Larregola
authors.forename: Shannon
authors.initials: S
authors.lastname: Moore
authors.forename: Nediljko
authors.initials: N
authors.lastname: Budisa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D049878:Mytilus / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins
chemical_list: D015815:Cell Adhesion Molecules; D011994:Recombinant Proteins; D011392:Proline