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 <i>Synechococcus</i> 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.