Karrikins force a rethink of strigolactone mode of action

Strigolactones (SL) and karrikins (KAR) both contain essential butenolide moieties, and both require the F-box protein MAX2 to control seed germination and photomorphogenesis in Arabidopsis thaliana. A new discovery that SL and KAR also require related α/β-hydrolase proteins for such activity suggests that they operate through a similar molecular mechanism. Based on structural similarity, a previously proposed mode of action for SL was also considered for KAR, but recent structure-activity studies suggest that this mechanism may not apply. Here we rationalise these observations into a hypothesis whereby different α/β-hydrolases distinguish SL and KAR by virtue of their non-butenolide moieties and catalyze nucleophilic attack on the butenolide. The products would be different for SL and KAR, and in the case of SL they have no biological activity. The inference is that nucleophilic attack on SL and KAR by α/β-hydrolases is required for their bioactivity, but the hydrolysis products are not.