Metabolomic analysis reveals rewiring of <scp><i>S</i></scp><i>ynechocystis</i> <scp>sp</scp>. <scp>PCC</scp> 6803 primary metabolism by <i>ntcA</i> overexpression

<jats:title>Summary</jats:title><jats:p><jats:styled-content style="fixed-case">NtcA</jats:styled-content> is a c<jats:styled-content style="fixed-case">AMP</jats:styled-content> receptor protein‐type transcription factor conserved among cyanobacteria and is essential for gene expression in response to nitrogen status. <jats:styled-content style="fixed-case">NtcA</jats:styled-content> has been widely studied; however, no metabolomic analysis has been conducted using the <jats:italic>ntcA</jats:italic> mutant. Here, we generated a strain that overexpresses <jats:italic>ntcA</jats:italic> in <jats:italic><jats:styled-content style="fixed-case">S</jats:styled-content>ynechocystis</jats:italic> sp. <jats:styled-content style="fixed-case">PCC</jats:styled-content> 6803, named <jats:styled-content style="fixed-case">NOX</jats:styled-content>10, and performed physiological, transcriptomic and metabolomic analyses. <jats:styled-content style="fixed-case">NOX</jats:styled-content>10 grew faster than the wild‐type strain under photoautotrophic conditions, but slower under light‐activated heterotrophic conditions. Transcriptome analysis revealed that the expression of genes related to primary metabolism was altered by <jats:italic>ntcA</jats:italic> overexpression particularly under nitrogen‐depleted conditions. Metabolomic analysis revealed that metabolite levels in sugar, purine/pyrimidine nucleotide, organic acid and amino acid metabolism were widely altered by <jats:italic>ntcA</jats:italic> overexpression. The protein levels of nitrogen‐regulated transcriptional regulators were altered by <jats:italic>ntcA</jats:italic> overexpression during nitrogen starvation. These results demonstrate the alteration of primary metabolism by genetic engineering of <jats:styled-content style="fixed-case">NtcA</jats:styled-content>, and they contribute to the current understanding of metabolic regulation of unicellular cyanobacteria.</jats:p>