<p><b><u>Book chapter postprint</u></b></p>\n\n<p><b>DOI: </b><a href="https://doi.org/10.1016/bs.abr.2015.08.005">10.1016/bs.abr.2015.08.005</a></p>\n\n<p><b>License:</b> <a href="http://sherpa.ac.uk/romeo/issn/0065-2296/">Sherpa/Romeo 0065-2296</a></p>\n\n<p> </p>\n\n<p><br></p><p><b>\nAbstract: </b>Cyclotides are gene-encoded, ribosomally produced cyclic proteins.\nTheir biosynthesis is a multistep process involving several enzymes for\ntranslation, disulphide isomerization, transport, cleavage and, finally,\ncyclization. Here, we describe this process, focusing on the cyclization step and\nthe vacuolar processing enzyme (VPE) that performs it.</p>\n\n<p>Cyclotide precursor proteins\ncontain prodomains that direct organelle targeting and contain sequences\nnecessary for cyclization in addition to the one or more domains that make up\nthe final cyclic product. The VPEs are a family of cysteine proteases that\nperform cyclization by an adaptation of their more commonly described\nproteolysis mechanism. VPE-mediated cyclization is dependent on the presence of\nshort recognition sequences (within and flanking the mature cyclotide domain)\nwhich have been characterized in vivo and in vitro for the prototypical\ncyclotide kalata B1. Finally, we compare cyclization by VPEs to other methods\nof protein cyclization found in nature or developed for biotechnology. Understanding\ncyclotide biosynthesis is important for both fundamental science, and for\nbroader protein cyclization applications.</p><div><div><p></p></div></div>