Intein-Mediated Biosynthesis of Bracelet Cyclotide

摘要

@@ Cyclotides are plant defense peptides with cyclic backbone cross-braced by three disulfide bonds in a knotted arrangement. They contain 28 to 37 amino acids and are mainly found in families of Rubiaceae and Violaceae. In general, they are stable to heating, resistant to enzyme digestion and thought to be orally bioactive. These properties make them potentially useful as drug candidates. Thus far more than 150 cyclotides have been identified and are categorized into three subfamilies bracelet, Mobius and hybrid (trypsin-inhibitor) based on sequence homology, structural variations and biochemical properties[1]. The bracelet cyclotide Hedyotide B1 is recently discovered from an herbal plant, Hedyotis biflora belonging to Rubiaceae family. It consists of 30 residues with+3 net-charge. Molecular modeling shows that its surface is amphipathic with hydrophobic patches to enable strong membrane-associated bacteriacidal activity. Here we describe a biosynthetic method to prepare bracelet cyclotide Hedyotide Bl by intem-mediated biosynthesis.