Comprehensive multifaceted gene network analysis towards understanding multi-metal and oxidative stress responses in...

Cyanobacteria, owing to their simple nutrient requirements, rapid growth, and well-sequenced genomes, are recognized as powerful systems for advancing research and for the bioremediation of environmental pollutants, including heavy metals and antibiotic residues. Among them, the widely studied Synechocystis sp. PCC 6803 serves as a well-established molecular chassis for diverse biotechnological applications. In this study, we explored the Synechocystis PCC 6803 transcriptomic data to decipher the multi-metal and oxidative stress-related gene co-expression networks and hub genes using the Weighted Gene Co-expression Network Analysis (WGCNA) tool. Our study revealed that cofactor biosynthesis, transcriptional regulatory proteins, efflux pumps, and the degradation of L-tryptophan and L-arginine constitute crucial responses of PCC 6803 specifically to H₂O₂ stress. Notably, the ABC-transporter functions prominently under Zn and Fe stress, where an ATP-independent periplasmic transporter was uniquely associated with Cd stress. In addition, the glutathione-mediated antioxidant defense was uniquely linked to Fe stress, carotenoid to both H₂O₂ and Zn stresses, and phosphorelay signalling to Fe and H₂O₂ stresses. Further, the DNA topoisomerase I and low-affinity CO₂ uptake proteins were identified as common hub proteins in both WGCNA and PPI analyses, critically responsive to H₂O₂ and Zn stresses, respectively. Our studies revealed shared and unique mechanisms orchestrated by Synechocystis PCC 6803 against different metals and oxidative stress, providing valuable insights into stress-tolerant strain engineering for various bioremediation applications.