DR. KEERTHANA PERUMAL,DR. HARISH MANOHARAN,DR. ARUN. M. S,DR. PRAKASH. D

DOI: https://doi.org/

The pressing need for sustainable and eco-friendly energy alternatives has propelled biological hydrogen (biohydrogen) production into the spotlight, with cyanobacteria emerging as promising microbial candidates due to their ability to perform oxygenic photosynthesis and fix atmospheric carbon dioxide. This review critically examines the metabolic pathways in cyanobacteria that are involved in hydrogen evolution, with a focus on [NiFe]-hydrogenases and nitrogenases. It highlights the major limitations hindering efficient hydrogen production, including oxygen sensitivity, electron flux competition, and regulatory bottlenecks. Advances in synthetic biology, metabolic engineering, and systems biology are explored as powerful tools for overcoming these challenges. Specific strategies such as knockout of competing pathways, redirection of reducing equivalents, promoter engineering, and heterologous expression of oxygen-tolerant hydrogenases are discussed in detail. Additionally, the review sheds light on integrative approaches using genome-scale modeling and omics data to rationally design optimized strains. Process-level improvements, including bioreactor innovations and light management systems, are also considered. Overall, this review emphasizes the critical role of multidisciplinary approaches in enhancing cyanobacterial biohydrogen yields and lays the groundwork for future developments toward industrial-scale biohydrogen production.