Induced Chemical Defense of a Mushroom by a Double‐Bond‐Shifting Polyene Synthase

The antilarval mushroom polyenes 18‐methyl‐19‐oxoicosaoctaenoic acid and 20‐methyl‐21‐oxodocosanonaenoic acid appear in response to injury of the mycelium of the stereaceous mushroom BY1. We identified a polyketide synthase (PPS1) which belongs to a hitherto completely uncharacterized clade of polyketide synthases. Expression of the PPS1 gene is massively upregulated following mycelial damage. The synthesis of the above polyenes was reconstituted in the mold Aspergillus niger as a heterologous host. This demonstrates that PPS1 1) synchronously produces branched‐chain polyketides of varied lengths, and 2) catalyzes the unprecedented shift of eight or nine double bonds. This study represents the first characterization of a reducing polyketide synthase from a mushroom. We also show that injury‐induced de novo synthesis of polyketides is a fungal response strategy. Shift work: The mushroom polyene synthase PPS1 produces the antilarval compounds 18‐methyl‐19‐oxoicosaoctaenoic and 20‐methyl‐21‐oxodocosanonaenoic acids simultaneously. PPS1 shifts the conjugated double bonds, as demonstrated by reconstituting synthase activity heterologously, and is induced by mycelial injury. The results suggest that de novo synthesis of the polyene is a chemical defense strategy of fungi.