Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms

Phytotransferrin, a functional analogue of transferrin, has an obligate requirement for carbonate to bind iron, which suggests that acidification-driven declines in the concentration of seawater carbonate ions may negatively affect diatom iron acquisition. Iron binding in phytoplankton Iron is an essential nutrient for photosynthetic plankton (phytoplankton), but owing to its low solubility in vast areas of the ocean the concentration of this metal is low, limiting the growth of the phytoplankton. Andrew Allen and co-workers show that the phytoplankton Phaeodactylum tricornutum has developed a specific iron acquisition mechanism that relies on activity of the ISIP2A protein. ISIP2A represents a functional analogue of transferrin—a metazoan protein that binds iron with high affinity—as both proteins use similar iron binding, internalization and release mechanisms, suggesting their independent and convergent evolution. Both proteins bind iron through a synergistic interaction of ferric iron and CO 3 2− , and because ocean acidification decreases CO 3 2− concentration it may also decrease phytoplankton iron uptake and growth. In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton 1 , 2 . Although most dissolved iron in the marine environment is complexed with organic molecules 3 , picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone 4 and serve as an important source of iron for eukaryotic phytoplankton and particularly for diatoms 5 . Genome-enabled studies of labile iron utilization by diatoms have previously revealed novel iron-responsive transcripts 6 , 7 , including the ferric iron-concentrating protein ISIP2A 8 , but the mechanism behind the acquisition of picomolar labile iron remains unknown. Here we show that ISIP2A is a phytotransferrin that independently and convergently evolved carbonate ion-coordinated ferric iron binding. Deletion of ISIP2A disrupts high-affinity iron uptake in the diatom Phaeodactylum tricornutum , and uptake is restored by complementation with human transferrin. ISIP2A is internalized by endocytosis, and manipulation of the seawater carbonic acid system reveals a second-order dependence on the concentrations of labile iron and carbonate ions. In P. tricornutum , the synergistic interaction of labile iron and carbonate ions occurs at environmentally relevant concentrations, revealing that carbonate availability co-limits iron upt