Characterization of an orphan biosynthetic gene cluster found in the fungus Aspergillus candidus CBS 102.13 resulted in the discovery of a pyrrolobenzazepine alkaloid, aspcandine (1). The unique molecular scaffold of 1 is synthesized by the nonribosomal peptide synthetase-polyketide synthase hybrid AcdB, which unusually incorporates 3-hydroxy-l-kynurenine as a building block. AcdB subsequently performs one round of chain elongation using malonyl-CoA, which is followed by the chain release to furnish the tricyclic system of 1.