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Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes.

Kastenmüller G, Schenk ME, Gasteiger J, Mewes HW - Genome Biol. (2009)

Bottom Line: Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics.Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale.Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse, Neuherberg, Germany. g.kastenmueller@helmholtz-muenchen.de

ABSTRACT
Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

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Degradation of histidine. The pathways glutamate fermentation (fnc1) (red) and degradation of histidine to L-glutamate (histidine2) (black) describe (amino acid) degradations producing ammonia as an end product. Due to the reversibility of all its reactions, this also includes the pathway of biosynthesis of 5-formimino-THF (blue), which - inversely followed - describes the degradation of 5-formimino-THF to glutamate (c2). All three pathways are interconnected and can be interpreted as complete degradation of L-histidine to acetate and ammonia (NH3). Thereby, three moles of ammonia per mole of histidine are produced (green or turquoise boxes, respectively). As histidine2 includes an alternative route from L-histidine to glutamate (dashed line), one mole of ammonia is either produced by the conversion of N-carbamoyl-L-glutamate to L-glutamate or by the conversion of N-formimino-tetrahydrofolate to 5,10-methenyl-tetrahydrofolate.
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Figure 9: Degradation of histidine. The pathways glutamate fermentation (fnc1) (red) and degradation of histidine to L-glutamate (histidine2) (black) describe (amino acid) degradations producing ammonia as an end product. Due to the reversibility of all its reactions, this also includes the pathway of biosynthesis of 5-formimino-THF (blue), which - inversely followed - describes the degradation of 5-formimino-THF to glutamate (c2). All three pathways are interconnected and can be interpreted as complete degradation of L-histidine to acetate and ammonia (NH3). Thereby, three moles of ammonia per mole of histidine are produced (green or turquoise boxes, respectively). As histidine2 includes an alternative route from L-histidine to glutamate (dashed line), one mole of ammonia is either produced by the conversion of N-carbamoyl-L-glutamate to L-glutamate or by the conversion of N-formimino-tetrahydrofolate to 5,10-methenyl-tetrahydrofolate.

Mentions: The three pathways glutamate fermentation (fnc1), degradation of histidine to L-glutamate (histidine2), and biosynthesis of 5-formimino-THF (c2) describe (amino acid) degradations producing ammonia as an end product and are predicted to be operative in the periodontal bacteria (except A. actinomycetemcomitans). Due to the reversibility of all its reactions, this also includes the pathway of biosynthesis of 5-formimino-THF, which - inversely followed - describes the degradation of 5-formimino-THF to glutamate. All three pathways are interconnected and can be interpreted as the complete degradation of L-histidine to acetate and (three moles) ammonia (NH3) (Figure 9). Studies by Niederman et al. [56] and Takahashi et al. [57] on ammonia as a mediator of periodontal infection support the biological relevance of our result. The authors showed that NH3 inhibits the polymorphonuclear leucocyte function of the host cells. It is known that this inhibition increases the susceptibility of humans to periodontal infection [58,59]. That ammonia plays an important role in periodontal disease is further supported by a study on the oral health of patients with chronic renal failure [60]. These patients show a higher prevalence of periodontal disease. Compared to healthy controls, a high concentration of urea is observed in the saliva of these patients. It is assumed that the increased amount of urea leads to an increased amount of ammonia due to the degradation of urea by urealytic oral bacteria such as Actinomyces naeslundii.


Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes.

Kastenmüller G, Schenk ME, Gasteiger J, Mewes HW - Genome Biol. (2009)

Degradation of histidine. The pathways glutamate fermentation (fnc1) (red) and degradation of histidine to L-glutamate (histidine2) (black) describe (amino acid) degradations producing ammonia as an end product. Due to the reversibility of all its reactions, this also includes the pathway of biosynthesis of 5-formimino-THF (blue), which - inversely followed - describes the degradation of 5-formimino-THF to glutamate (c2). All three pathways are interconnected and can be interpreted as complete degradation of L-histidine to acetate and ammonia (NH3). Thereby, three moles of ammonia per mole of histidine are produced (green or turquoise boxes, respectively). As histidine2 includes an alternative route from L-histidine to glutamate (dashed line), one mole of ammonia is either produced by the conversion of N-carbamoyl-L-glutamate to L-glutamate or by the conversion of N-formimino-tetrahydrofolate to 5,10-methenyl-tetrahydrofolate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2690999&req=5

Figure 9: Degradation of histidine. The pathways glutamate fermentation (fnc1) (red) and degradation of histidine to L-glutamate (histidine2) (black) describe (amino acid) degradations producing ammonia as an end product. Due to the reversibility of all its reactions, this also includes the pathway of biosynthesis of 5-formimino-THF (blue), which - inversely followed - describes the degradation of 5-formimino-THF to glutamate (c2). All three pathways are interconnected and can be interpreted as complete degradation of L-histidine to acetate and ammonia (NH3). Thereby, three moles of ammonia per mole of histidine are produced (green or turquoise boxes, respectively). As histidine2 includes an alternative route from L-histidine to glutamate (dashed line), one mole of ammonia is either produced by the conversion of N-carbamoyl-L-glutamate to L-glutamate or by the conversion of N-formimino-tetrahydrofolate to 5,10-methenyl-tetrahydrofolate.
Mentions: The three pathways glutamate fermentation (fnc1), degradation of histidine to L-glutamate (histidine2), and biosynthesis of 5-formimino-THF (c2) describe (amino acid) degradations producing ammonia as an end product and are predicted to be operative in the periodontal bacteria (except A. actinomycetemcomitans). Due to the reversibility of all its reactions, this also includes the pathway of biosynthesis of 5-formimino-THF, which - inversely followed - describes the degradation of 5-formimino-THF to glutamate. All three pathways are interconnected and can be interpreted as the complete degradation of L-histidine to acetate and (three moles) ammonia (NH3) (Figure 9). Studies by Niederman et al. [56] and Takahashi et al. [57] on ammonia as a mediator of periodontal infection support the biological relevance of our result. The authors showed that NH3 inhibits the polymorphonuclear leucocyte function of the host cells. It is known that this inhibition increases the susceptibility of humans to periodontal infection [58,59]. That ammonia plays an important role in periodontal disease is further supported by a study on the oral health of patients with chronic renal failure [60]. These patients show a higher prevalence of periodontal disease. Compared to healthy controls, a high concentration of urea is observed in the saliva of these patients. It is assumed that the increased amount of urea leads to an increased amount of ammonia due to the degradation of urea by urealytic oral bacteria such as Actinomyces naeslundii.

Bottom Line: Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics.Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale.Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse, Neuherberg, Germany. g.kastenmueller@helmholtz-muenchen.de

ABSTRACT
Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

Show MeSH
Related in: MedlinePlus