The rice seedling blight fungus Rhizopus microsporus harbors endosymbiotic bacteria (Burkholderia rhizoxinica) that produce the virulence factor rhizoxin and control host development. Genome mining indicated a massive inventory of cryptic non-ribosomal peptide synthetase (NRPS) genes, which have not yet been linked to any natural products. We report the discovery and full characterization of a novel cyclopeptide from endofungal bacteria. In silico analysis of an orphan, symbiont-specific NRPS predicted the structure of a nonribosomal peptide, which was targeted by LC-MS/MS profiling of wild type and engineered null mutants. NMR and chemical derivatization elucidated the structure of the bacterial cyclopeptide. Phylogenies revealed the relationship starter C domains for rare N-acetyl capped peptides. Heptarhizin is produced under symbiotic conditions in geographically constrained strains from the Pacific clade, indicating a potential ecological role of the peptide.