We have
identified 4 AFT1-regulated genes (ARN1-4) by cDNA
microarray analysis that encodes siderophore transporters. Our data
indicate that siderophore uptake in budding yeast occurs through two
different pathways, an intracellular pathway that requires Arn
proteins and a plasma membrane-based pathway that requires the
high-affinity ferrous-iron transporter. Uptake of siderophore-bound
iron through the ferrous-specific transporter is likely to require the
activity of a siderophore-iron reductase. FRE1 and FRE2
encode ferric-and cupric-reductases and are required for ferric iron
uptake. S. cerevisiae expresses five other genes homologous to
FRE1 and FRE2, four of which are regulated by iron and
Aft1p. We questioned whether members of the FRE gene family
encode siderophore reductases. In the absence of the Arn transporters,
FRE3 and, to a lesser extent, FRE1 and/or FRE2
were involved in utilization of iron bound to siderophores of the
hydroxamate class. Fre3p is 76% identical to Fre2p. Deletion of
FRE3 resulted in diminished growth on ferrioxamine B,
ferrichrome, and triacetylfusarinine C as well as diminished uptake of
iron bound to these siderophores. Budding yeast expressed ferrioxamine
B reductase activity that was diminished in a fre1 fre2 strain
and was undetectable in a fre1 fre2 fre3 strain. FRE1,
2, and 3 were not required for siderophore uptake through
the ARN-dependent pathway. Other FRE genes may be
required for reduction of other classes of siderophores.
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