Prochlorococcus phage ferredoxin: structural characterization and interactions with cyanobacterial sulfite reductases

Marine cyanobacteria are infected by phage whose genomes encode ferredoxin (Fd) electron carriers. While these Fds are thought to redirect the energy harvested from light to phage-encoded oxidoreductases that enhance viral fitness, it is not clear how the biochemical and biophysical properties of phage Fds relate to those in photosynthetic organisms. Bioinformatic analysis using a sequence similarity network revealed that phage Fds display the highest similarity with cyanobacterial Fds that transfer electrons from photosystems to oxidoreductases involved in nutrient assimilation. Structural analysis of myovirus P-SSM2 Fd (pssm2-Fd), which infects Prochlorrococcus marinus, revealed high similarity to cyanobacterial Fds (≤0.5A RMSD). Additionally, pssm2-Fd exhibits a low midpoint reduction potential (-336 mV vs. SHE) similar to other photosynthetic Fds, albeit lower thermostability (Tm = 29°C) than many Fds. When expressed in an Escherichia coli strain with a sulfite assimilation defect, pssm2-Fd complemented growth when coexpressed with a Prochlorrococcus marinus sulfite reductase, revealing that pssm2-Fd can transfer electrons to a host sulfite reductase. The high structural similarity with cyanobacterial Fds and cross reactivity with sulfite reductase suggests that phage Fds evolved to transfer electrons to both phage- and cyanobacterial-encoded oxidoreductases.