Book chapter postprint
License: Sherpa/Romeo 0065-2296
Abstract: Cyclotides are gene-encoded, ribosomally produced cyclic proteins.
Their biosynthesis is a multistep process involving several enzymes for
translation, disulphide isomerization, transport, cleavage and, finally,
cyclization. Here, we describe this process, focusing on the cyclization step and
the vacuolar processing enzyme (VPE) that performs it.
Cyclotide precursor proteins
contain prodomains that direct organelle targeting and contain sequences
necessary for cyclization in addition to the one or more domains that make up
the final cyclic product. The VPEs are a family of cysteine proteases that
perform cyclization by an adaptation of their more commonly described
proteolysis mechanism. VPE-mediated cyclization is dependent on the presence of
short recognition sequences (within and flanking the mature cyclotide domain)
which have been characterized in vivo and in vitro for the prototypical
cyclotide kalata B1. Finally, we compare cyclization by VPEs to other methods
of protein cyclization found in nature or developed for biotechnology. Understanding
cyclotide biosynthesis is important for both fundamental science, and for
broader protein cyclization applications.