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Journal of Bacteriology, August 2000, p. 4146-4152, Vol. 182, No. 15
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Two Active Forms of UDP-N-Acetylglucosamine Enolpyruvyl Transferase in Gram-Positive Bacteria

Wensheng Du,dagger James R. Brown, Daniel R. Sylvester, Jianzhong Huang, Alison F. Chalker, Chi Y. So, David J. Holmes, David J. Payne, and Nicola G. Wallis*

Anti-Infectives Research, SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania 19426

Received 23 February 2000/Accepted 11 May 2000

Gene sequences encoding the enzymes UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from many bacterial sources were analyzed. It was shown that whereas gram-negative bacteria have only one murA gene, gram-positive bacteria have two distinct genes encoding these enzymes which have possibly arisen from gene duplication. The two murA genes of the gram-positive organism Streptococcus pneumoniae were studied further. Each of the murA genes was individually inactivated by allelic replacement. In each case, the organism was viable despite losing one of its murA genes. However, when attempts were made to construct a double-deletion strain, no mutants were obtained. This indicates that both genes encode active enzymes that can substitute for each other, but that the presence of a MurA function is essential to the organism. The two genes were further cloned and overexpressed, and the enzymes they encode were purified. Both enzymes catalyzed the transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetylglucosamine, confirming they are both active UDP-N-acetylglucosamine enolpyruvyl transferases. The catalytic parameters of the two enzymes were similar, and they were both inhibited by the antibiotic fosfomycin.

* Corresponding author. Mailing address: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, Collegeville, PA 19426. Phone: (610) 917-6352. Fax: (610) 917-7901. E-mail: Nicola_G_Wallis{at}sbphrd.com.

dagger Present address: Lead Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06705.

Journal of Bacteriology, August 2000, p. 4146-4152, Vol. 182, No. 15
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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