Adaptive Laboratory Evolution in Synechocystis sp. PCC 6803: Current Status and Perspectives.

With the increasing environmental concerns about carbon dioxide emissions and the pressing demand for sustainable resources, photosynthetic microorganisms have gained considerable attention as alternative platforms for the environmentally friendly production of fuels and chemicals. These organisms function as green cell factories capable of directly converting carbon dioxide into organic carbon metabolites using solar energy, offering a promising platform for more sustainable biomanufacturing. Among these organisms, cyanobacteria, and particularly Synechocystis sp. PCC 6803, have emerged as particularly attractive hosts due to their relatively simple cellular organization, efficient photosynthetic metabolism, and amenability to genetic manipulation. In addition to rational metabolic engineering approaches, Adaptive Laboratory Evolution (ALE) has recently been proposed as a powerful strategy to improve Synechocystis strain robustness, enhance tolerance to environmental and metabolic stresses, and optimize cellular performance under specific growth conditions. By selecting beneficial spontaneous mutations over successive generations, ALE could complement genetic engineering strategies and further expand the potential of cyanobacterial platforms for efficient and sustainable bioproduction.