Outlook on Synthetic Biology-Driven Hydrogen Production: Lessons from Algal Photosynthesis Applied to Cyanobacteria

Photobiological hydrogen production offers a sustainable route to clean energy by harnessing solar energy through photosynthetic microorganisms. The pioneering sulfur-deprivation technique developed by Melis and colleagues in the green alga Chlamydomonas reinhardtii successfully enabled sustained hydrogen production by downregulating photosystem II (PSII) activity to reduce oxygen evolution, creating anaerobic conditions necessary for hydrogenase activity. Inspired by this approach, we present the project of the European consortium PhotoSynH2, which builds on these biological insights and employs synthetic biology to replicate and enhance this strategy in cyanobacteria, specifically, Synechocystis sp. PCC 6803. By genetically engineering precise downregulation of PSII, we aim to reduce oxygen evolution without the unintended effects associated with nutrient deprivation, enabling efficient hydrogen production. Additionally, re-engineering endogenous respiration to continuously replenish glycogen consumed during respiration allows matching oxygen production with consumption, maintaining anaerobic conditions conducive to hydrogen production. This review discusses how focusing on molecular-level processes and leveraging advanced genetic tools can lead to a new methodology that potentially offers improved results over traditional approaches. By redirecting electron flow and optimizing redox pathways, we seek to enhance hydrogen production efficiency in cyanobacteria. Our approach demonstrates how harnessing photosynthesis through synthetic biology can contribute to scalable and sustainable hydrogen production, addressing the growing demand for renewable energy and advancing toward a carbon-neutral future.