Biosynthesis of the fungal nonribosomal peptide penilumamide A and biochemical characterization of a pterin-specific adenylation domain

We report the characterization of the penilumamide biosynthetic cluster from Aspergillus flavipes CNL-338. In vitro reconstitution experiments demonstrated that three nonribosomal peptide synthetases are required for constructing the tripeptide and studies with dissected adenylation domains allowed for the first biochemical characterization of a domain that selects a pterin-derived building block. The first biosynthetic characterization of a lumazine-containing nonribosomal peptide and the biochemical investigation of the respective adenylation domains is described.