Cyclic hexapeptide fusahexin features a unique fused 6,5-bicyclic N,O-acetal, the biosynthetic origin of which is unresolved. Metabolomics analysis of a gene deletion in Fusarium graminearum revealed an Orn-containing intermediate, prefusahexin, as the product of nonribosomal peptide synthetase NRPS4. The chemical structure of prefusahexin was verified by total synthesis, and its predicted oxidized intermediate was synthesized and cyclized to fusahexin. These results establish prefusahexin as the key biosynthetic precursor to fusahexin.
Natola et al. (2026) studied this question.