Formation of the Fungal Indole Alkaloid Speradine F Implies Multiple Nonenzymatic Oxidation Steps.

The highly oxygenated indole alkaloid speradine F () with a 6/5/6/5/5/5 hexacyclic skeleton was isolated from a culture of , together with its precursors β-cyclopiazonic acid (β-CPA, ) and cyclopiazonic acid (CPA, ). Gene deletion and heterologous expression led to the identification of the responsible five-gene cluster for the speradine skeleton formation. Precursor supply experiments proved that was enzymatically converted, via 2-oxoCPA (), to speradine A (), which subsequently undergoes multistep nonenzymatic hydroxylations to .