title: ADP-ribosylation as an intermediate step in inactivation of rifampin by a mycobacterial gene.
abstract: Mycobacterium smegmatis DSM43756 inactivates rifampin, and the inactivated antibiotic product recovered from culture medium was ribosylated on the 23-OH group. To study this process, the gene responsible for the inactivation was expressed at high levels by the lac promoter in Escherichia coli conferring resistance to >500 microg of antibiotic per ml. Cell homogenates generated a novel derivative designated RIP-TAs; in this study, we determined that RIP-TAs is 23-(O-ADP-ribosyl)rifampin. Our results indicated that RIP-TAs is an intermediate in the pathway leading to ribosylated rifampin and that the previously characterized gene encodes a mono(ADP-ribosyl)transferase which, however, shows no sequence similarity to other enzymes of this class.
authors.affiliation: Genetics Department, University of the Witwatersrand, Johannesburg 2050, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Quan
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: K
authors.initials: K
authors.lastname: Yazawa
authors.forename: E R
authors.initials: ER
authors.lastname: Dabbs
authors.forename: N
authors.initials: N
authors.lastname: Morisaki
authors.forename: S
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Furihata
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D000904:Antibiotics, Antitubercular / Q000378:metabolism* / Q000494:pharmacology; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D007763:Lac Operon; D009682:Magnetic Resonance Spectroscopy; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012293:Rifampin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000904:Antibiotics, Antitubercular; D036002:ADP Ribose Transferases; D012293:Rifampin