Genetic evidence for the importance of protein acetylation and protein deacetylation in the halophilic archaeon Haloferax volcanii

Protein acetylation and deacetylation reactions are involved in many regulatory processes in eukaryotes. Recently, it was found that similar processes occur in bacteria and archaea. Sequence analysis of the genome of the haloarchaeon Haloferax volcanii led to the identification of three putative protein acetyltransferases belonging to the Gcn5 family, Patl, Pat2, and Elp3, and two deacetylases, Sir2 and Hdal. Intriguingly, the gene that encodes Hdal shares an operon with an archaeal histone homolog. We performed gene knockouts to determine whether the genes encoding these putative acetyltransferases and deacetylases are essential. A sir2 deletion mutant was able to grow normally, whereas an hdal deletion mutant was nonviable. The latter is consistent with the finding that trichostatin A, a specific inhibitor of Hdal, inhibits cell growth in a concentration-dependent manner. We also showed that each of the acetyltransferases by itself is dispensable for growth but that deletion of both pat2 and elp3 could not be achieved. The corresponding genes are therefore "synthetic lethals," and the protein acetyltransferases probably have a common and essential substrate.