ZmaR, a novel and widespread antibiotic resistance determinant that acetylates zwittermicin A.

Abstract:

:ZmaR is a resistance determinant of unusual abundance in the environment and confers on gram-positive and gram-negative bacteria resistance to zwittermicin A, a novel broad-spectrum antibiotic produced by species of Bacillus. The ZmaR protein has no sequence similarity to proteins of known function; thus, the purpose of the present study was to determine the function of ZmaR in vitro. Cell extracts of E. coli containing zmaR inactivated zwittermicin A by covalent modification. Chemical analysis of inactivated zwittermicin A by 1H NMR, 13C NMR, and high- and low-resolution mass spectrometry demonstrated that the inactivated zwittermicin A was acetylated. Purified ZmaR protein inactivated zwittermicin A, and biochemical assays for acetyltransferase activity with [14C]acetyl coenzyme A demonstrated that ZmaR catalyzes the acetylation of zwittermicin A with acetyl coenzyme A as a donor group, suggesting that ZmaR may constitute a new class of acetyltransferases. Our results allow us to assign a biochemical function to a resistance protein that has no sequence similarity to proteins of known function, contributing fundamental knowledge to the fields of antibiotic resistance and protein function.

journal_name

J Bacteriol

journal_title

Journal of bacteriology

authors

Stohl EA,Brady SF,Clardy J,Handelsman J

doi

10.1128/JB.181.17.5455-5460.1999

keywords:

subject

Has Abstract

pub_date

1999-09-01 00:00:00

pages

5455-60

issue

17

eissn

0021-9193

issn

1098-5530

journal_volume

181

pub_type

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