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In vivo production of catalase containing haem analogues.

Brugna, Myriam LU ; Tasse, Lena and Hederstedt, Lars LU (2010) In The FEBS Journal 277(12). p.2663-2672
Abstract
Haem (protohaem IX) analogues are toxic compounds and have been considered for use as antibacterial agents, but the primary mechanism behind their toxicity has not been demonstrated. Using the haem protein catalase in the Gram-positive bacterium Enterococcus faecalis as an experimental system, we show that a variety of haem analogues can be taken up by bacterial cells and incorporated into haem-dependent enzymes. The resulting cofactor-substituted proteins are dysfunctional, generally resulting in arrested cell growth or death. This largely explains the cell toxicity of haem analogues. In contrast to many other organisms, E. faecalis does not depend on haem for growth, and therefore resists the toxicity of many haem analogues. We have... (More)
Haem (protohaem IX) analogues are toxic compounds and have been considered for use as antibacterial agents, but the primary mechanism behind their toxicity has not been demonstrated. Using the haem protein catalase in the Gram-positive bacterium Enterococcus faecalis as an experimental system, we show that a variety of haem analogues can be taken up by bacterial cells and incorporated into haem-dependent enzymes. The resulting cofactor-substituted proteins are dysfunctional, generally resulting in arrested cell growth or death. This largely explains the cell toxicity of haem analogues. In contrast to many other organisms, E. faecalis does not depend on haem for growth, and therefore resists the toxicity of many haem analogues. We have exploited this feature to establish a bacterial in vivo system for the production of cofactor-substituted haem protein variants. As a pilot study, we produced, isolated and analysed novel catalase variants in which the iron atom of the haem prosthetic group is replaced by other metals, i.e. cobalt, gallium, tin, and zinc, and also variants containing meso-protoheme IX, ruthenium meso-protoporphyrin IX and (metal-free) protoporphyrin IX. Engineered haem proteins of this type are of potential use within basic research and the biotechnical industry. Structured digital abstract * MINT-7722358, MINT-7722368: katA (uniprotkb:Q834P5) and katA (uniprotkb:Q834P5) physically interact (MI:0915) by copurification (MI:0025). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Enterococcus faecalis, antibacterial agents, catalase, haem protein, metal porphyrins
in
The FEBS Journal
volume
277
issue
12
pages
2663 - 2672
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000278307800008
  • scopus:77953185280
ISSN
1742-464X
DOI
10.1111/j.1742-4658.2010.07677.x
language
English
LU publication?
yes
id
12d11968-949f-47d2-9e9a-76dab7681a4b (old id 1610032)
date added to LUP
2010-06-14 15:24:16
date last changed
2018-05-29 11:36:46
@article{12d11968-949f-47d2-9e9a-76dab7681a4b,
  abstract     = {Haem (protohaem IX) analogues are toxic compounds and have been considered for use as antibacterial agents, but the primary mechanism behind their toxicity has not been demonstrated. Using the haem protein catalase in the Gram-positive bacterium Enterococcus faecalis as an experimental system, we show that a variety of haem analogues can be taken up by bacterial cells and incorporated into haem-dependent enzymes. The resulting cofactor-substituted proteins are dysfunctional, generally resulting in arrested cell growth or death. This largely explains the cell toxicity of haem analogues. In contrast to many other organisms, E. faecalis does not depend on haem for growth, and therefore resists the toxicity of many haem analogues. We have exploited this feature to establish a bacterial in vivo system for the production of cofactor-substituted haem protein variants. As a pilot study, we produced, isolated and analysed novel catalase variants in which the iron atom of the haem prosthetic group is replaced by other metals, i.e. cobalt, gallium, tin, and zinc, and also variants containing meso-protoheme IX, ruthenium meso-protoporphyrin IX and (metal-free) protoporphyrin IX. Engineered haem proteins of this type are of potential use within basic research and the biotechnical industry. Structured digital abstract * MINT-7722358, MINT-7722368: katA (uniprotkb:Q834P5) and katA (uniprotkb:Q834P5) physically interact (MI:0915) by copurification (MI:0025).},
  author       = {Brugna, Myriam and Tasse, Lena and Hederstedt, Lars},
  issn         = {1742-464X},
  keyword      = {Enterococcus faecalis,antibacterial agents,catalase,haem protein,metal porphyrins},
  language     = {eng},
  number       = {12},
  pages        = {2663--2672},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {The FEBS Journal},
  title        = {In vivo production of catalase containing haem analogues.},
  url          = {http://dx.doi.org/10.1111/j.1742-4658.2010.07677.x},
  volume       = {277},
  year         = {2010},
}