MDPI Acta Medica Okayama 2223-7747 13 15 2024 Light-Driven H2 Production in Chlamydomonas reinhardtii: Lessons from Engineering of Photosynthesis 2114 EN Michael Hippler Institute of Plant Science and Resources, Okayama University Fatemeh Khosravitabar Department of Biological and Environmental Sciences, University of Gothenburg In the green alga Chlamydomonas reinhardtii, hydrogen production is catalyzed via the [FeFe]-hydrogenases HydA1 and HydA2. The electrons required for the catalysis are transferred from ferredoxin (FDX) towards the hydrogenases. In the light, ferredoxin receives its electrons from photosystem I (PSI) so that H-2 production becomes a fully light-driven process. HydA1 and HydA2 are highly O-2 sensitive; consequently, the formation of H-2 occurs mainly under anoxic conditions. Yet, photo-H-2 production is tightly coupled to the efficiency of photosynthetic electron transport and linked to the photosynthetic control via the Cyt b(6)f complex, the control of electron transfer at the level of photosystem II (PSII) and the structural remodeling of photosystem I (PSI). These processes also determine the efficiency of linear (LEF) and cyclic electron flow (CEF). The latter is competitive with H-2 photoproduction. Additionally, the CBB cycle competes with H-2 photoproduction. Consequently, an in-depth understanding of light-driven H-2 production via photosynthetic electron transfer and its competition with CO2 fixation is essential for improving photo-H-2 production. At the same time, the smart design of photo-H-2 production schemes and photo-H-2 bioreactors are challenges for efficient up-scaling of light-driven photo-H-2 production. No potential conflict of interest relevant to this article was reported.