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Antimicrobial Agents and Chemotherapy, January 1999, p. 181-184, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

ADP-Ribosylation as an Intermediate Step in Inactivation of Rifampin by a Mycobacterial Gene

Selwyn Quan,1 Tamae Imai,2 Yuzuru Mikami,2,* Katsukiyo Yazawa,2 Eric R. Dabbs,1 Naoko Morisaki,3 Shigeo Iwasaki,3,dagger Yuichi Hashimoto,3 and Kazuo Furihata4

Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chuo-ku, Chiba 260-8673,2 Institute of Molecular and Cellular Biosciences3 and Department of Agricultural Chemistry,4 University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan, and Genetics Department, University of the Witwatersrand, Johannesburg 2050, South Africa1

Received 9 March 1998/Returned for modification 20 October 1998/Accepted 4 November 1998

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 µg 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.


* Corresponding author. Mailing address: Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8673, Japan. Phone: 81-43-222-7171, ext. 5923. Fax: 81-43-226-2486. E-mail: mikami{at}myco.pf.chiba-u.ac.jp.

dagger Present address: The Kitasato Institute, 5-9-1, Shirokane, Minato-ku, Tokyo 108, Japan.


Antimicrobial Agents and Chemotherapy, January 1999, p. 181-184, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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