Biosynthesis of a Fully Functional Cyclotide inside Living Bacterial Cells

Abstract

Perfect circle. We report the biosynthesis of a natively folded cyclotide, MCoTI-II, in E. coli by intracellular backbone cyclization of a linear cyclotide–intein fusion precursor. The cyclized peptide then spontaneously folds into its native conformation. Biosynthetic access to correctly folded cyclotides allows the possibility of generating cell-based combinatorial libraries that can be screened, inside living cells, for their ability to modulate or inhibit cellular processes. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2007/z700183_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.