Cooperative Biocatalysis Enables Assembly of a Prenylated Indole Alkaloid

Abstract

The hapalindole‐type metabolites have garnered significant interest due to their diverse biological activities and unique chemical structures. Recently, the biosynthesis of this family of indole alkaloids has been uncovered and shown to involve a rare biocatalytic Cope rearrangement. Previously, we demonstrated cis‐indole isonitrile C‐3 normal geranylation using FamD2. Thus, we sought to explore further the reaction potential with this substrate and dimethylallyl pyrophosphate (DMAPP) using prenyltransferases and cyclases from the hapalindole biosynthetic pathways. Here, we report a new compound derived from an unexpected biosynthetic Cope rearrangement, which expands further the scope of metabolites generated from cyanobacterial Stig cyclases.