Cyclotide synthesis and supply: from plant to bioprocess

Cyclotides are disulfide-rich miniproteins with a circular backbone and a knotted arrangement ofdisulfide bonds. Because these plant-derived peptides are resistant to degradation and exhibit a diverse range of bioactivity they have become important agronomic and industrial objectives. They belong to a group of compounds with low market volume and high price that are poorly processed by microorganisms, are too complex for economic chemical synthesis, and thus are valuable candidates for the synthesis in plant cell bioprocesses. This review highlights current research aimed at production routes of cyclotides in Oldenlandia affinis plantlets and cell cultures, and summarizes recent advances in bioprocessing aspects, with particular emphasis on the development of suitable bioreactor configurations for plant cell culture-based processes, the optimization of culture environments as a powerful means to improve yields, bioreactor operational modes, and trends in protein recovery.