Interplay between the bacterial protein deacetylase CobB and the second messenger c‐di‐GMP

As a ubiquitous bacterial secondary messenger, c‐di‐GMP plays key regulatory roles in processes such as bacterial motility and transcription regulation. CobB is the Sir2 family protein deacetylase that controls energy metabolism, chemotaxis, and DNA supercoiling in many bacteria. Using an Escherichia coli proteome microarray, we found that c‐di‐GMP strongly binds to CobB. Further, protein deacetylation assays showed that c‐di‐GMP inhibits the activity of CobB and thereby modulates the biogenesis of acetyl‐CoA. Interestingly, we also found that one of the key enzymes directly involved in c‐di‐GMP production, DgcZ, is a substrate of CobB. Deacetylation of DgcZ by CobB enhances its activity and thus the production of c‐di‐GMP. Our work establishes a novel negative feedback loop linking c‐di‐GMP biogenesis and CobB‐mediated protein deacetylation. Synopsis The bacterial secondary messenger c‐di‐GMP plays key regulatory roles in processes such as bacterial motility and transcription regulation. This study reveals a negative feedback loop between c‐di‐GMP biogenesis and CobB‐dependent protein deacetylation. An Escherichia coli proteome‐wide microarray identifies deacetylase CobB as a c‐di‐GMP‐binding protein. c‐di‐GMP binding inhibits deacetylase activity of CobB. CobB deacetylates and activates diguanylate cyclase DgcZ. DgcZ deacetylation promotes c‐di‐GMP production. Graphical Abstract A negative feedback loop between c‐di‐GMP production and the Escherichia coli Sir2‐family deacetylase CobB modulates biogenesis of acetyl‐CoA.