Abstract
Abstract
Folates are essential metabolites of the cell and need to be acquired either by transport or biosynthesis. All metazoa including humans, some bacteria, and some protozoa acquire it solely through specific transporters. Plants and fungi, in contrast, have the capacity both for de novo biosynthesis and for uptake through plasma membrane folate transporters. These recently identified transporters belong to the oligopeptide transporter (OPT) family. Folate transporters from this family have been identified in yeasts and other fungi, including pathogenic fungi. They have also been observed in plants such as Arabidopsis thaliana and have the ability to transport both synthetic and natural folates including the naturally abundant 5-methyl tetrahydrofolate. In Saccharomyces cerevisiae, the folate transporter Opt1p (Hgt1p) is a proton-coupled transporter that was already known to transport glutathione (GSH). While in some organisms a single transporter is able to transport both substrates, in other organisms separate transporters in this family exist for folate and GSH. Mutational, kinetic, and functional studies of S. cerevisiae Opt1p have identified residues involved in substrate translocation, including those specific for folate or GSH recognition, as well as for proton-coupled transport. These studies suggest, in analogy to a human proton-coupled folate transporter and a plant OPT family phytosiderophore transporter, HvYS1, that proton-driven folate transport follows an alternating access mechanism with features described here. These transporters have implications for drug development strategies targeting the folate pathway of fungi and have importance in folate biofortification strategies for crops.