Phosphorus deficiency alleviates cyanobacterial iron-limitation through a direct PhoB_x0002_ mediated gene regulation

Iron (Fe) and phosphorus (P) are essential nutrients with close geochemical association. They exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. However, the adaptive strategies of photosynthetic organisms to Fe/P co-limitation remain largely unknown. Here, we show that phosphorus deficiency increases the growth of Fe-limited cyanobacteria through a PhoB-mediated regulatory network. In addition to its well-recognized role in controlling phosphate homeostasis, PhoB regulates key metabolic processes crucial for Fe-limited cyanobacteria, including ROS detoxification and Fe uptake. Transcript abundances of PhoB-targeted genes are enriched in samples from the P-deplete ocean, and a conserved PhoB binding site is widely present in the promoters of the targets, suggesting that the strategy we discovered may be highly conserved. Our findings provide important molecular insights into the response of cyanobacteria to simultaneous Fe/P nutrient limitation and help in understanding how nutrient availability affects primary productivity in aquatic environments. The phoB-FLAG3 strains were grown in phosphate limited medium to an OD730 of 0.5 and then cross-linked by 1% formaldehyde treatment for 15 min at room temperature,followed by quenching with 125 mM glycine. Sample preparation for ChIP-Seq was performed as previously described and libraries were prepared from two biological replicates. The library sequencing was performed with Illumina NovaSeq 6000 by IGENEBOOK Biotechnology Co., Ltd. The MACS2 program (version 2.1.1.20160309) was used for peak calling, and the data were visualized by IGV (version 2.16.0)