Cyclopenol
(1) and viridicatol (6) with m-hydroxyl groups were isolated from a culture of Penicillium
palitans. Genome mining and heterologous
expression in Aspergillus nidulans led
to the identification of their biosynthetic gene cluster and the cytochrome
P450 enzyme VdoD responsible for the meta hydroxylation.
Precursor feeding experiments into vdoD transformant
proved the conversion of cyclopenin (2) to 1, which then undergoes a spontaneous or VdoA-catalyzed rearrangement
to 6. A direct conversion of viridicatin (5) to 6 by VdoD was not detected.
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.
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