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Chapter 20 : General Metabolism and Biochemical Pathways of Tubercle Bacilli

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Abstract:

This chapter focuses on the postgenomic advances, where a functional understanding of the genes and pathways predicted for intermediary metabolism in the complex has been obtained, as the framework for the chapter. An interesting spectrum of attenuation was obtained, from very slight in mutants with mutations in sulfur amino acid biosynthesis through strongly attenuated for proline, tryptophan, and leucine auxotrophs to lethal deletions that could not be rescued by the addition of amino acids to culture media for aspartokinase and for the gene in the shared part of aromatic amino biosynthesis. The principal carbon sources that are supplied to in culture are glucose, glycerol, lipids, and the carbon skeletons of amino acids. Regardless of which are used, they must be both dissimilated, via acetyl-CoA, to provide energy, and assimilated, notably into the copious glycans and lipids that characterize the mycobacteria. The publication of the annotated genome sequence has provided the basis for renewed interest in its metabolism. All the annotated genes have been modeled into biochemical pathways, and functional genomics has already provided new insights into its physiology, its regulation, and its relation to virulence. Patterns are already emerging, with genes involved in stress response, lipid catabolism, and anaerobiosis being linked to the persistence of tubercle bacilli. Together with biochemical demonstrations to verify suggested metabolic pathways or confirmation that individual genes encode key enzymes, these approaches provide a powerful weapon against the tubercle bacilli.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20

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Aromatic Amino Acid Biosynthesis
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Nuclear Magnetic Resonance Spectroscopy
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Figure 1

Biosynthesis of the aspartate family of amino acids. Unbroken arrows show chemical transformations, and broken arrows show pathways of several transformations.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Image of Figure 2
Figure 2

Branched chain amino acid biosynthesis. Unbroken arrows show chemical transformations, and broken arrows show pathways of several transformations.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Figure 3

Sulfur metabolism—cysteine. Unbroken arrows show chemical transformations, and broken arrows show pathways of several transformations.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Figure 4

Sulfur metabolism—methionine. Unbroken arrows show chemical transformations, and broken arrows show pathways of several transformations.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Image of Figure 5
Figure 5

Carbon metabolism and its links to metabolism in general, including lipid metabolism. Unbroken arrows show chemical transformations, and broken arrows show pathways of several transformations. OAA, oxaloacetate; PEP, phosphopyruvate.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Image of Figure 6
Figure 6

Carbon metabolism and its relation to cell wall biosynthesis. Unbroken arrows show chemical transformations, and broken arrows show pathways of several transformations.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Image of Figure 7
Figure 7

Respiration of . Electron flow is shown by unbroken arrows; broken arrows are used to show three other metabolic steps linking involved substrates.

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
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Tables

Generic image for table
Table 1

Genes in biosynthesis of the aspartate family of amino acids

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
Generic image for table
Table 2

Genes in branched chain amino acid biosynthesis

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
Generic image for table
Table 3

Genes in sulfur metabolism—cysteine

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
Generic image for table
Table 4

Genes in sulfur metabolism—methionine

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
Generic image for table
Table 6

Biosynthesis of monomers for cell envelope glycans and glycolipids

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
Generic image for table
Table 5

Genes in pathways of carbon metabolism

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20
Generic image for table
Table 7

Energy generation: genes for electron transport components

Citation: Wheeler P, Blanchard J. 2005. General Metabolism and Biochemical Pathways of Tubercle Bacilli, p 309-340. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch20

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