Synthesis of Serine, Glycine, Cysteine, and Methionine

Frank J. Grundy; Tina Μ. Henkin

doi:10.1128/9781555817992.ch18

Chapter 18 : Synthesis of Serine, Glycine, Cysteine, and Methionine

Authors: Frank J. Grundy, Tina Μ. Henkin

Content Type: Monograph

Publication Year: 2002

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555817992

Chapter DOI: 10.1128/9781555817992.ch18

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Abstract:

Methionine and cysteine are the two sulfur-containing amino acids, and cysteine biosynthesis represents the primary pathway for incorporation of organic sulfur into cellular components. Synthesis of the sulfur-containing amino acids is connected to central metabolism through the precursors serine, glycine, and homoserine. In addition to its general function as a component of proteins, methionine is specifically required for translation initiation and is crucial to a variety of methyltransferase reactions, both as a precursor of S-adenosylmethionine (SAM) and in tetrahydrofolate (THF) metabolism. The primary pathway for glycine generation in bacteria is through the interconversion of serine and glycine by L-serine hydroxymethyltransferase, encoded by glyA. Conversion of serine to glycine also provides N5,N10-methylene-THF, which is reduced by N5,N10-methylene-THF reductase to generate N5-methyl-THF for use in the conversion of homocysteine to methionine; this step regenerates the THF required for glycine production. In the major route of methionine biosynthesis, the backbone of methionine is derived from homoserine, and the sulfur moiety is derived from cysteine. Utilization of SAM as methyl donor results in formation of S-adenosylhomocysteine (SAH), whereas during polyamine biosynthesis SAM is first decarboxylated by the speD gene product, after which spermidine synthase catalyzes its reaction with putrescine to yield spermidine and methylthioadenosine (MTA). Homocysteine derived from SAH can be reconverted to methionine by methionine synthase, while methylthioribose (MTR) in Escherichia coli is excreted. The coupling of genomic sequence data with information about known physiological properties of the organism and regulatory insights provides a unique opportunity to identify putative genes and pathways.

Citation: Grundy F, Henkin T. 2002. Synthesis of Serine, Glycine, Cysteine, and Methionine, p 245-254. In Sonenshein A, Losick R, Hoch J (ed), Bacillus subtilis and Its Closest Relatives. ASM Press, Washington, DC. doi: 10.1128/9781555817992.ch18

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Synthesis of Serine, Glycine, Cysteine, and Methionine

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FIGURE 1

Cysteine and methionine metabolic pathways. Genes that are linked to S-box or T-box regulatory elements are shown with a boxed S or T, respectively. The amino acid corresponding to the T-box element specifier sequence is shown to the right in single-letter abbreviation. An asterisk to the left of the boxed S or Τ indicates genes that contain S- or T-box leaders in other gram-positive species (see Table 1 ). All other genes are those of B. subtilis except those in parentheses, which are Escherichia coli genes that have no apparent homologs in B. subtilis. B. subtilis genes starting with “y” are genes whose function has not been experimentally established. hipO was previously named only on the basis of homology. Genes in brackets are second copies of genes whose function has already been investigated. Only ATPs that contribute more than a phosphate moiety are shown. Abbreviations not found in the text: α-KB, α-ketobutyrate; O-AH, O-acetylhomoserine; KMTB, ketomethylthiobutyrate.

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FIGURE 1

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FIGURE 2

S-box and T-box transcription termination control mechanisms. (A) S-box system. During growth in the presence of methionine, a regulatory factor (dotted ellipse) binds to the upstream stem-loop of the leader RNA in response to methonine or some other effector (box). Binding stabilizes the anti-antiterminator form of the leader, preventing formation of the antiterminator form, permitting termination. When methionine is limiting, the anti-antiterminator is destabilized, permitting formation of the antiterminator and transcription of the downstream genes (arrow). All genes in the family respond to methionine availability. T, terminator; AT, antiterminator; AAT, anti-antiterminator. (B) T-box system. When charging of the cognate tRNA is high, the charged tRNA (with box representing the amino acid) binds by codon-anticodon pairing to the specifier sequence in the leader RNA but is unable to stabilize the antiterminator so that the terminator forms. Uncharged tRNA can interact with both the specifier sequence and the side-bulge of the antiterminator, stabilizing the antiterminator and preventing termination. Each gene in the family responds individually to the charging ratio of its cognate tRNA, with specificity primarily directed by the identity of the codon at the position of the specifier sequence. S, specifier sequence; Τ, T-box sequence, which forms the 5′ part of the antiterminator.

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FIGURE 2

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Tables

Synthesis of Serine, Glycine, Cysteine, and Methionine

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TABLE 1

Genes for biosynthesis of serine, glycine, cysteine, and methionine

a Downward arrow indicates direction of transcription of clustered genes. All B. subtilis gene locations and sequence features are based on the SubtiList database (http://genolist.pasteur.fr/SubtiList); information for E. coli was obtained from the Colibri database (http://genolist.pasteur.fr/Colibri), and sequence information for other gram-positive organisms was obtained through The Institute for Genomic Research Microbial Database (http://www.tigr.org/tdb/mdb/mdbinprogress.html).

b Equivalent gene where known in E. coli if the gene name differs from that of B. subtilis.

c ylnD corresponds to the 3′ region of E. coli cysG; ylnF corresponds to the 5' region of E. coli cysG.

d T-box (Thr) in Clostridium difficile.

e This step is catalyzed by homoserine O-succinyltransferase in E. coli.

f S-box gene in Clostridium acetobutylicum.

g T-box (met) in Staphylococcus aureus.

h This enzyme, which bypasses yjcI and yjcJ, is found in Clostridium and Brevibacterium spp. but not in B. subtilis or E. coli.

i The metH form of methionine synthase is found in Clostridium sp. but not in B. subtilis.

j yitJ contains a homocysteine binding domain at its 5′ end, absent in E. coli metF.

k T-box (Met) in C. difficile.

l T-box (Cys) in C. difficile.

m T-box (Met) in Enterococcus faecalis.

n S-box in Bacillus anthacis.

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TABLE 1

Genes for biosynthesis of serine, glycine, cysteine, and methionine

b Equivalent gene where known in E. coli if the gene name differs from that of B. subtilis.

c ylnD corresponds to the 3′ region of E. coli cysG; ylnF corresponds to the 5' region of E. coli cysG.

d T-box (Thr) in Clostridium difficile.

e This step is catalyzed by homoserine O-succinyltransferase in E. coli.

f S-box gene in Clostridium acetobutylicum.

g T-box (met) in Staphylococcus aureus.

h This enzyme, which bypasses yjcI and yjcJ, is found in Clostridium and Brevibacterium spp. but not in B. subtilis or E. coli.

i The metH form of methionine synthase is found in Clostridium sp. but not in B. subtilis.

j yitJ contains a homocysteine binding domain at its 5′ end, absent in E. coli metF.

k T-box (Met) in C. difficile.

l T-box (Cys) in C. difficile.

m T-box (Met) in Enterococcus faecalis.

n S-box in Bacillus anthacis.