title: Glutamate racemase is an endogenous DNA gyrase inhibitor.
abstract: Almost all bacteria possess glutamate racemase to synthesize d-glutamate as an essential component of peptidoglycans in the cell walls. The enforced production of glutamate racemase, however, resulted in suppression of cell proliferation. In the Escherichia coli JM109/pGR3 clone, the overproducer of glutamate racemase, the copy number (i.e. replication efficiency) of plasmid DNA declined dramatically, whereas the E. coli WM335 mutant that is defective in the gene of glutamate racemase showed little genetic competency. The comparatively low and high activities for DNA supercoiling were contained in the E. coli JM109/pGR3 and WM335 cells, respectively. Furthermore, we found that the DNA gyrase of E. coli was modulated by the glutamate racemase of E. coli in the presence of UDP-N-acetylmuramyl-l-alanine, which is a peptidoglycan precursor and functions as an absolute activator for the racemase. This is the first finding of the enzyme protein participating in both d-amino acid metabolism and DNA processing.
authors.affiliation: Department of Bioresources Science, Kochi University, Nankoku, Kochi 783-8502, Japan. ashiuchi@cc.kochi-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ashiuchi
authors.forename: Eriko
authors.initials: E
authors.lastname: Kuwana
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kazuya
authors.initials: K
authors.lastname: Komatsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Soda
authors.forename: Haruo
authors.initials: H
authors.lastname: Misono
mesh_terms: D000591:Amino Acid Isomerases / Q000737:chemistry* / Q000502:physiology*; D002384:Catalysis; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D027081:DNA Gyrase / Q000378:metabolism*; D004278:DNA, Superhelical; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism; D005822:Genetic Vectors; D010457:Peptidoglycan / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D015854:Up-Regulation; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D004278:DNA, Superhelical; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C076606:UDP-N-acetylmuramylalanine; D004247:DNA; D000591:Amino Acid Isomerases; C062292:glutamate racemase; D027081:DNA Gyrase