Several species of filamentous cyanobacteria of the genus Nostoc are known to accumulate metabolites with interesting biological activities. In addition, cyanobacteria culture processes in closed photobioreactors currently make it possible to increase biomass and/or metabolite productivity. The strain Nostoc sp ATCC 53789 is known to produce cryptophycin (Cr). This cyclo-depsipeptide, identified as one of the most tubulin-destabilizing agents, is experiencing a recent revival of interest, due to antibody-drug-conjugate (ADC) type developments. Then, as part of the Anr CrytoGreen program, one of the objectives is to increase biomass and Cryptophycin productivity by minimizing the ecological footprint of the process. Compared with previous studies where the nitrogen source was nitrate, the present study shows that switching to a diazotrophic culture mode results in an equivalent intracellular accumulation of Cry. A stoichiometric analysis improved the composition of the BG11 culture medium. Theoretical conversion yield values are determined for comparison with data obtained in the photobioreactor. This step reveals the importance of phosphate inputs to ensure biomass and production where only incident light fluxes are limiting. Optimal pH and temperature are also determined thanks to chemostat cultures. The highest productivities are obtained when the cyanobacteria cultures are pre-adapted to light fluxes of up to 500 µmoles quanta m-2 s-1. Moreover, the formation of heterocysts, the cells that fix atmospheric nitrogen in an aerobic environment, is associated with the capacity of filament aggregation. This property makes it possible to harvest biomass using a simple decantation/filtration process. All these data are used to design an eco-friendly process based on semi-continuous production.