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

Author:

Quan Selwyn1,Imai Tamae2,Mikami Yuzuru2,Yazawa Katsukiyo2,Dabbs Eric R.1,Morisaki Naoko3,Iwasaki Shigeo3,Hashimoto Yuichi3,Furihata Kazuo4

Affiliation:

1. Genetics Department, University of the Witwatersrand, Johannesburg 2050, South Africa1

2. Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chuo-ku, Chiba 260-8673,2

3. Institute of Molecular and Cellular Biosciences3 and

4. Department of Agricultural Chemistry,4 University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan, and

Abstract

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 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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