Aspcandine: A Pyrrolobenzazepine Alkaloid Synthesized by a Fungal Nonribosomal Peptide Synthetase-Polyketide Synthase Hybrid

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.

Automated summary

Characterization of a biosynthetic gene cluster in the fungus Aspergillus candidus CBS 102.13 led to the discovery of a new alkaloid, aspcandine (1). The unique molecular scaffold of aspcandine (1) is synthesized by the nonribosomal peptide synthetase-polyketide synthase hybrid AcdB, which incorporates 3-hydroxy-L-kynurenine as a building block. AcdB performs chain elongation using malonyl-CoA and releases the chain to form the tricyclic system of aspcandine (1).