Very high CO₂ concentrations inhibit photosynthesis and trigger transcriptomic stress responses in cyanobacteria

CO[Formula: see text] concentrations above air level (0.04%) are beneficial for the growth of cyanobacteria. However, very high CO[Formula: see text] levels inhibit growth, limiting the usability of cyanobacteria for carbon capture and biotechnological applications. The transcriptomic changes in the cyanobacterium Synechococcus sp. PCC 7002 were investigated at varying growth rates governed by different gas-phase CO[Formula: see text] concentrations, ranging from limiting (0.04%) to optimal (4% and 8%) to inhibitory high (30%). Compared to optimal CO[Formula: see text] concentrations, large differences in the transcriptome were observed in limiting and inhibiting CO[Formula: see text]. At 30% CO[Formula: see text], genes encoding CO[Formula: see text] uptake mechanisms, photosynthetic electron transfer, and light-harvesting antennae proteins were down-regulated compared to lower CO[Formula: see text]. Genes involved in the ribosomal machinery and biosynthetic pathways were down-regulated at 30% and 0.04% CO[Formula: see text], consistent with the observed reduced growth. The genes most strongly up-regulated at 30% CO[Formula: see text] were primarily associated with stress responses, but did not closely resemble the transcriptomic changes at other stress conditions previously described. The small RNA PsrR1 was strongly up-regulated at 30% CO[Formula: see text] and is likely to be involved in the regulation of growth. These transcriptomic insights are essential for the engineering of fast-growing cyanobacteria at high CO[Formula: see text], which can be applied in carbon capture from industrial point sources.