Study of Metyltetraprole, an unusual agrofungicide targeting the Q o -site of cytochrome bc 1 complex

Abstract The mitochondrial respiratory chain bc 1 complex is a proven target of agrofungicides. Most of them are Q o -site antagonists ( i . e QoIs), competing with the substrate ubiquinol, and likely share the same binding mode as the widespread Q o -site resistance mutation G143A confers cross-resistance. Metyltetraprole (MTP) presents an exception as studies with phytopathogenic fungi showed that the inhibitor was unaffected by G143A. Here, we used the yeast model to investigate its mode of action. Analysis of bc 1 complex mutants supports a Q o -site binding for MTP. However the compound seems distinct to other QoIs, such as azoxystrobin, in various ways, namely; 1) G143A was without effect on MTP, as previously reported. 2) The level of MTP resistance of mutants was higher in bc 1 complex activity assays than in growth assays while the opposite was observed with azoxystrobin. 3) Steady-state kinetics used to characterise the mode of action of MTP also revealed differences compared to other QoIs.