Enzymatic Benzofuranoindoline Formation in the Biosynthesis of the Strained Bridgehead Bicyclic Dipeptide (+)‐Azonazine A

Abstract We uncovered and reconstituted a concise biosynthetic pathway of the strained dipeptide (+)‐azonazine A from marine‐derived Aspergillus insulicola . Formation of the hexacyclic benzofuranoindoline ring system from cyclo‐( l ‐Trp‐ N ‐methyl‐ l ‐Tyr) is catalyzed by a P450 enzyme through an oxidative cyclization. Supplementing the producing strain with various indole‐substituted tryptophan derivatives resulted in the generation of a series of azonazine A analogs.