ADP-ribosylation as an intermediate step in inactivation of rifampin by a mycobacterial gene.
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.
Quan
S
S
Genetics Department, University of the Witwatersrand, Johannesburg 2050, South Africa.
Imai
T
T
Mikami
Y
Y
Yazawa
K
K
Dabbs
E R
ER
Morisaki
N
N
Iwasaki
S
S
Hashimoto
Y
Y
Furihata
K
K
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
D000904:Antibiotics, Antitubercular; D036002:ADP Ribose Transferases; D012293:Rifampin