New insights into the function of the proteins IsiC and IsiD from Synechocystis sp. PCC 6803 under iron limitation.

Iron is a common cofactor in biological processes such as respiration, photosynthesis, and nitrogen fixation. The genes isiC and isiD encode unknown proteins, and the growth of ΔisiC and ΔisiD mutants is inhibited under iron-deficient conditions. To study the regulatory mechanisms of IsiC and IsiD during iron starvation, we carried out transcriptome and metabolome sequencing. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the photosynthesis, nitrogen metabolism, and ABC transporter pathways play a vital role in regulating iron deficiency. Upon iron repletion, IsiC and IsiD also have a regulatory effect on these pathways. Additionally, KEGG analysis of the differential metabolites of wild type (WT) and mutants showed that they were all enriched in starch and sucrose metabolism after iron limitation. Weighted gene co-expression network analysis (WGCNA) constructed a co-expression network of differentially expressed genes with phenotypes and metabolites, and finally identified five modules. The turquoise module was positively correlated with iron deficiency. In contrast, the WT and blue module exhibited a negative correlation, and the mutants ΔisiC and ΔisiD were positively correlated with the gray and brown modules, respectively. WGCNA also analyzed the relationship between metabolites and phenotypes, and the green module was related to iron starvation. The co-expression network determined the hub genes and metabolites of each module. This study lays a foundation for a better understanding of cyanobacteria in response to iron deficiency. KEY POINTS: • Nitrogen metabolism and ABC transporters are involved in iron regulation. • Starch and sucrose metabolism is related to the regulation of iron deficiency. • WGCNA analyzes the correlation between genes and metabolites.