Photobiological Hydrogen Production in Cyanobacteria: Advances, Challenges, and Perspectives

Hydrogen molecules can serve as a promising clean energy supplier; conventional hydrogen production usually relies on fossil fuels and leads to intense greenhouse gas emissions. Significant emphasis has been placed on exploring sustainable and renewable hydrogen resources. Cyanobacteria can convert solar energy into hydrogen through oxygen-sensitive hydrogenases or nitrogenases. However, practical application remains severely constrained by oxygen-evolving photosynthesis, inefficient electron allocation, and the low metabolic priority of hydrogen production in cyanobacterial cells. In recent years, substantial progress has been achieved in understanding hydrogen metabolism and improving hydrogen production through physiological regulation, hydrogenase engineering, photosynthetic electron transport chain (PETC) reconstruction, metabolic engineering, and biohybrid systems. This review summarizes recent advances in cyanobacterial hydrogen production, with particular emphasis on hydrogen-producing pathways, key limiting factors, and current engineering strategies. Importantly, this review highlights that many currently reported strategies still provide only transient improvements because hydrogen production is constrained by system-level conflicts among photosynthesis, redox balance, carbon fixation, and cellular stability. In addition, emerging approaches including metagenomic resource mining, synthetic biology, AI-assisted engineering, biohybrid photoelectrochemical systems, and techno-economic optimization are discussed as potential directions for improving the efficiency, scalability, and practical feasibility of cyanobacterial hydrogen production technologies in the future.