The isoprenyl chain length of coenzyme Q mediates the nutritional resistance of fungi to amoeba predation.

Unlabelled: Amoebae are environmental predators feeding on bacteria, fungi, and other eukaryotic microbes. Predatory interactions alter microbial communities and impose selective pressure toward phagocytic resistance or escape which may, in turn, foster virulence attributes. The ubiquitous fungivorous amoeba has a wide prey spectrum in the fungal kingdom but discriminates against members of the clade, such as and . Here, we show that this prey discrimination among fungi is solely based on the presence of ubiquinone as an essential cofactor for the predator. While the amoeba readily fed on fungi with CoQ presenting longer isoprenyl side chain variants CoQ8-10, such as those from the clade, it failed to proliferate on those with shorter CoQ variants, specifically from the clade (CoQ6). Supplementing non-edible yeast with CoQ9 or CoQ10 rescued the growth , highlighting the importance of a long isoprenyl side chain. Heterologous biosynthesis of CoQ9 in by introducing genes responsible for CoQ9 production from the evolutionary more basic complemented the function of the native CoQ6. The results suggest that the use of CoQ6 among members of the clade might have originated as a predatory escape strategy in fungal lineages and could be retained in organisms that were able to thrive by fermentation.

Importance: Ubiquinones (CoQ) are universal electron carriers in the respiratory chain of all aerobic bacteria and eukaryotes. Usually 8-10 isoprenyl units ensure their localization within the lipid bilayer. Members of the clade among fungi are unique in using only 6. The reason for this is unclear. Here we provide evidence that the use of CoQ6 efficiently protects these fungi from predation by the ubiquitous fungivorous amoeba which lacks its own biosynthetic pathway for this vitamin. The amoebae were starving on a diet of CoQ6 yeasts which could be complemented by either the addition of longer CoQs or the genetic engineering of a CoQ9 biosynthetic pathway.