title: DNA adenine hypomethylation leads to metabolic rewiring in Deinococcus radiodurans.
abstract: The protein encoded by DR_0643 gene from Deinococcus radiodurans was shown to be an active N-6 adenine-specific DNA methyltransferase (Dam). Deletion of corresponding protein reduced adenine methylation in the genome by 60% and resulted in slow-growth phenotype. Proteomic changes induced by DNA adenine hypomethylation were mapped by two-dimensional protein electrophoresis coupled with mass spectrometry. As compared to wild type D. radiodurans cells, at least 54 proteins were differentially expressed in Δdam mutant. Among these, 39 metabolic enzymes were differentially expressed in Δdam mutant. The most prominent change was DNA adenine hypomethylation induced de-repression of pyruvate dehydrogenase complex, E1 component (aceE) gene resulting in 10 fold increase in the abundance of corresponding protein. The observed differential expression profile of metabolic enzymes included increased abundance of enzymes involved in fatty acid and amino acid degradation to replenish acetyl Co-A and TCA cycle intermediates and diversion of phosphoenolpyruvate and pyruvate into amino acid biosynthesis, a metabolic rewiring attempt by Δdam mutant to restore energy generation via glycolysis-TCA cycle axis. This is the first report of DNA adenine hypomethylation mediated rewiring of metabolic pathways in prokaryotes.
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India; Department of Zoology, Centre for Advanced Studies, University of Pune, Pune 411007, India.
authors.forename: Nayana S
authors.initials: NS
authors.lastname: Shaiwale
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Bhakti
authors.initials: B
authors.lastname: Basu
authors.affiliation: Department of Zoology, Centre for Advanced Studies, University of Pune, Pune 411007, India.
authors.forename: Deepti D
authors.initials: DD
authors.lastname: Deobagkar
authors.affiliation: Department of Zoology, Centre for Advanced Studies, University of Pune, Pune 411007, India.
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Deobagkar
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. Electronic address: aptesk@barc.gov.in.
authors.forename: Shree K
authors.initials: SK
authors.lastname: Apte
mesh_terms: D000225:Adenine / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D034301:Deinococcus / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D008745:Methylation; D040901:Proteomics; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; C058693:Dam methyltransferase; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D000225:Adenine
keywords: Adenine methyltransferase; DNA adenine methylation; Deinococcus radiodurans; Metabolic rewiring; Pyruvate dehydrogenase