Biosynthesis of the fungal metabolite, piliformic acid (2-hexylidene-3-methylsuccinic acid)

Abstract

The biosynthesis of piliformic acid, a secondary metabolite of various xylariaceous fungi, has been studied in Poronia piliformis and Xylaria mali. The metabolite can be retro-biosynthetically cleaved to generate a C₈ and a C₃ moiety. The study reveals that the C₈ unit is derived directly from octanoate and that the octanoate in turn originates from a fatty acid synthase (FAS) rather than from a polyketide synthase (PKS). This conclusion is drawn after assaying the stereochemical course of the enoyl reductase involved in the synthesis of the octanoate unit. The C₃ unit is efficiently labelled by succinate and the citric acid cycle intermediate oxaloacetate is implicated as a key biosynthetic precursor. The location of deuterium after isotopic labelling with sodium [²H₁₅]octanoate reveals a 1,3-hydrogen shift, indicative of a double-bond isomerisation, operating at a late stage in the biosynthesis. A hypothesis for piliformic acid biosynthesis is presented and discussed in the context of structurally related fungal and lichen metabolites.