Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes

G.J.E. Baart, B. Zomer, A. de Haan, L.A. van der Pol, E.C. Beuvery, J. Tramper, D.E. Martens

Research output: Contribution to journalReview articleAcademicpeer-review

56 Citations (Scopus)

Abstract

Background - Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Results - Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures. Conclusion - The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.
Original languageEnglish
Pages (from-to)R136
JournalGenome Biology
Volume8
Issue number7
DOIs
Publication statusPublished - 2007

Fingerprint

Neisseria meningitidis
chemostat
genome
metabolism
Genome
modeling
Metabolic Networks and Pathways
substrate preference
disability
vaccine
pathogenicity
antigen
cleavage
Serogroup B Neisseria meningitidis
genomics
pathogen
culture media
Neisseria
phosphate
Pentose Phosphate Pathway

Keywords

  • c14 labelled glucose
  • bombardment mass-spectrometry
  • biochemical reaction systems
  • linear constraint relations
  • serum bactericidal activity
  • membrane vesicle vaccine
  • gram-negative bacteria
  • escherichia-coli
  • meningococcal disease
  • genus neisseria

Cite this

Baart, G.J.E. ; Zomer, B. ; de Haan, A. ; van der Pol, L.A. ; Beuvery, E.C. ; Tramper, J. ; Martens, D.E. / Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes. In: Genome Biology. 2007 ; Vol. 8, No. 7. pp. R136.
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abstract = "Background - Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Results - Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures. Conclusion - The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69{\%}) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.",
keywords = "c14 labelled glucose, bombardment mass-spectrometry, biochemical reaction systems, linear constraint relations, serum bactericidal activity, membrane vesicle vaccine, gram-negative bacteria, escherichia-coli, meningococcal disease, genus neisseria",
author = "G.J.E. Baart and B. Zomer and {de Haan}, A. and {van der Pol}, L.A. and E.C. Beuvery and J. Tramper and D.E. Martens",
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doi = "10.1186/gb-2007-8-7-r136",
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Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes. / Baart, G.J.E.; Zomer, B.; de Haan, A.; van der Pol, L.A.; Beuvery, E.C.; Tramper, J.; Martens, D.E.

In: Genome Biology, Vol. 8, No. 7, 2007, p. R136.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes

AU - Baart, G.J.E.

AU - Zomer, B.

AU - de Haan, A.

AU - van der Pol, L.A.

AU - Beuvery, E.C.

AU - Tramper, J.

AU - Martens, D.E.

PY - 2007

Y1 - 2007

N2 - Background - Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Results - Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures. Conclusion - The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.

AB - Background - Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Results - Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures. Conclusion - The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.

KW - c14 labelled glucose

KW - bombardment mass-spectrometry

KW - biochemical reaction systems

KW - linear constraint relations

KW - serum bactericidal activity

KW - membrane vesicle vaccine

KW - gram-negative bacteria

KW - escherichia-coli

KW - meningococcal disease

KW - genus neisseria

U2 - 10.1186/gb-2007-8-7-r136

DO - 10.1186/gb-2007-8-7-r136

M3 - Review article

VL - 8

SP - R136

JO - Genome Biology

JF - Genome Biology

SN - 1474-7596

IS - 7

ER -