Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 421, Issue 4, Pages 646-650Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.04.031
Keywords
Bio-adhesive; Genetic code engineering; Mussel foot protein; Fluoroproline; Hydroxyproline
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Funding
- Bavarian Research Foundation
- Whitaker International Fellows and Scholars Program
- UniCat Excellence Cluster of the Berlin Institute of Technology
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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. (C) 2012 Elsevier Inc. All rights reserved.
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