Small, cyclic peptides are reported to have many bioactivities. In bacteria and fungi, they can be made by nonribosomal peptide synthetases, but in plants they are exclusively ribosomal. Cyclic peptides from the Annona genus possess cytotoxic and anti-inflammatory activities, but their biosynthesis is unknown. The medicinal soursop plant, Annona muricata, contains annomuricatins A (cyclo-PGFVSA) and B (cyclo-PNAWLGT). Here, using de novo transcriptomics and tandem mass spectrometry, we identify a suite of short transcripts for precursor proteins for 10 validated annomuricatins, 9 of which are novel. In their precursors, annomuricatins are preceded by an absolutely conserved Glu and each peptide sequence has a conserved proto-C-terminal Pro, revealing parallels with the segetalin orbitides from the seed of Vaccaria hispanica, which are processed through ligation by a prolyl oligopeptidase in a transpeptidation reaction.