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While elevated CO\n                      <jats:sub>2<\/jats:sub>\n                      levels generally promote growth, excessively high levels inhibit growth through uncertain mechanisms. This study investigated the physiology of the cyanobacterium\n                      <jats:italic>Synechocystis<\/jats:italic>\n                      sp. PCC 6803 under very high CO\n                      <jats:sub>2<\/jats:sub>\n                      concentrations and yet stable pH around 7.5. The growth rate of the wild type (WT) at 200\u00a0\u00b5mol photons m\n                      <jats:sup>\u22122<\/jats:sup>\n                      \u00a0s\n                      <jats:sup>\u22121<\/jats:sup>\n                      and a gas phase containing 30% CO\n                      <jats:sub>2<\/jats:sub>\n                      was 2.7-fold lower compared to 4% CO\n                      <jats:sub>2<\/jats:sub>\n                      . Using a CRISPR interference mutant library, we identified genes that, when repressed, either enhanced or impaired growth under 30% or 4% CO\n                      <jats:sub>2<\/jats:sub>\n                      . Repression of genes involved in light harvesting (\n                      <jats:italic>cpc<\/jats:italic>\n                      and\n                      <jats:italic>apc<\/jats:italic>\n                      ), photochemical electron transfer (\n                      <jats:italic>cytM<\/jats:italic>\n                      ,\n                      <jats:italic>psbJ<\/jats:italic>\n                      , and\n                      <jats:italic>petE<\/jats:italic>\n                      ), and several genes with little or unknown functions promoted growth under 30% CO\n                      <jats:sub>2<\/jats:sub>\n                      , while repression of key regulators of photosynthesis (\n                      <jats:italic>pmgA<\/jats:italic>\n                      ) and CO\n                      <jats:sub>2<\/jats:sub>\n                      capture and fixation (\n                      <jats:italic>ccmR<\/jats:italic>\n                      ,\n                      <jats:italic>cp12<\/jats:italic>\n                      , and\n                      <jats:italic>yfr1<\/jats:italic>\n                      ) increased growth inhibition under 30% CO\n                      <jats:sub>2<\/jats:sub>\n                      . Experiments confirmed that WT cells were more susceptible to light inhibition under 30% than under 4% CO\n                      <jats:sub>2<\/jats:sub>\n                      and that a light-harvesting-impaired \u0394\n                      <jats:italic>cpcG<\/jats:italic>\n                      mutant showed improved growth under 30% CO\n                      <jats:sub>2<\/jats:sub>\n                      compared to the WT. These findings suggest that enhanced fitness under very high CO\n                      <jats:sub>2<\/jats:sub>\n                      involves modifications in light harvesting, electron transfer, and carbon metabolism, and that the native regulatory machinery is insufficient, and in some cases obstructive, for optimal growth under 30% CO\n                      <jats:sub>2<\/jats:sub>\n                      . This genetic profiling provides potential targets for engineering cyanobacteria with improved photosynthetic efficiency and stress resilience for biotechnological applications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Synechocystis growth was inhibited under very high CO<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>2<\/jats:italic>\n                      <\/jats:sub>\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Inhibition of growth under very high CO<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>2<\/jats:italic>\n                      <\/jats:sub>\n                      <jats:italic>was light dependent.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Repression of photosynthesis genes improved growth under very high CO<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>2<\/jats:italic>\n                      <\/jats:sub>\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-025-13416-2","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T04:32:09Z","timestamp":1738211529000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Photosynthesis in Synechocystis sp. 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