Global cyclotide adventure: a journey dedicated to the discovery of circular peptides from flowering plants.

Circular peptides and proteins of great number and diversity have been discovered in bacteria, plants, and animals. Cyclotides--disulfide-knotted and head-to-tail cyclized plant peptides that exhibit various bioactivities--are by far the largest group of circular proteins. Since their first discovery over three decades ago, there has been a lot of progress in the elucidation of structural characteristics and applications of cyclotides as novel peptide drug grafting frameworks, but there is a lack of information about their native occurrence in various plant families. The "global cyclotide adventure" was initiated as a plant collection and analysis project to advance our understanding of the origin and distribution of cyclotides in flowering plants. Here, I will provide a chronological overview of the preparation of this project, including background information on plant taxonomy and morphology, summarize, and comment on the recent progress about the discovery of cyclotide-producing plants and will give an outlook on the future of cyclotide analysis and further discoveries to be made.