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

The highly oxygenated indole alkaloid speradine F ( 4 ) with a 6/5/6/5/5/5 hexacyclic skeleton was isolated from a culture of Penicillium palitans , together with its precursors β-cyclopiazonic acid (β-CPA, 5 ) and cyclopiazonic acid (CPA, 1 ). Gene deletion and heterologous expression led to the identification of the responsible five-gene spe cluster for the speradine skeleton formation. Precursor supply experiments proved that 1 was enzymatically converted, via 2-oxoCPA ( 2 ), to speradine A ( 3 ), which subsequently undergoes multistep nonenzymatic hydroxylations to 4 .