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Journal of Bacteriology, December 2000, p. 6783-6790, Vol. 182, No. 23
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Degradation of Heme in Gram-Negative Bacteria: the Product of the hemO Gene of Neisseriae Is a Heme Oxygenase

Wenming Zhu,1 Angela Wilks,2 and Igor Stojiljkovic1,*

Department of Microbiology and Immunology, Emory School of Medicine, Atlanta, Georgia 30322,1 and Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 212012

Received 11 July 2000/Accepted 3 September 2000

A full-length heme oxygenase gene from the gram-negative pathogen Neisseria meningitidis was cloned and expressed in Escherichia coli. Expression of the enzyme yielded soluble catalytically active protein and caused accumulation of biliverdin within the E. coli cells. The purified HemO forms a 1:1 complex with heme and has a heme protein spectrum similar to that previously reported for the purified heme oxygenase (HmuO) from the gram-positive pathogen Corynebacterium diphtheriae and for eukaryotic heme oxygenases. The overall sequence identity between HemO and these heme oxygenases is, however, low. In the presence of ascorbate or the human NADPH cytochrome P450 reductase system, the heme-HemO complex is converted to ferric-biliverdin IXalpha and carbon monoxide as the final products. Homologs of the hemO gene were identified and characterized in six commensal Neisseria isolates, Neisseria lactamica, Neisseria subflava, Neisseria flava, Neisseria polysacchareae, Neisseria kochii, and Neisseria cinerea. All HemO orthologs shared between 95 and 98% identity in amino acid sequences with functionally important residues being completely conserved. This is the first heme oxygenase identified in a gram-negative pathogen. The identification of HemO as a heme oxygenase provides further evidence that oxidative cleavage of the heme is the mechanism by which some bacteria acquire iron for further use.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory School of Medicine, Atlanta, GA 30322. Phone: (404) 727-1322. Fax: (404) 727-8250. E-mail: stojiljk{at}microbio.emory.edu.

Journal of Bacteriology, December 2000, p. 6783-6790, Vol. 182, No. 23
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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