Abstract Cyanobacteria are photosynthetic prokaryotes of high ecological and biotechnological relevance that have been cultivated in laboratories around the world for more than 70 years. Prolonged laboratory culturing has led to multiple microevolutionary events and the appearance of a large number of ‘domesticated’ substrains among model cyanobacteria. Despite its widespread occurrence, strain domestication is still largely ignored. In this work we describe Synechococcus elongatus PCC 7942‐KU, a novel domesticated substrain of the model cyanobacterium S. elongatus PCC 7942, which presents a fast‐sedimenting phenotype. Under higher ionic strengths the sedimentation rate increased leading to complete sedimentation in just 12 h. Through whole genome sequencing and gene deletion, we demonstrated that the Group 3 alternative sigma factor F plays a key role in cell sedimentation. Further analysis showed that significant changes in cell surface structures and a three‐fold increase in released polysaccharides lead to the appearance of a fast‐sedimenting phenotype. This work sheds light on the determinants of the planktonic to benthic transitions and provides genetic targets to generate fast‐sedimenting strains that could unlock cost‐effective cyanobacterial harvesting at scale.
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