|Description||Methionine and cysteine are the two sulfur-containing amino acids, and cysteine biosynthesis constitutes the primary pathway for incorporation of organic sulfur into cellular components. Cysteine serves as a precursor for methionine biosynthesis via the Transsulfuration pathway. Alternative pathway for methionine biosynthesis, the Sulfhydrylation pathway, use inorganic sulfur instead of cysteine. In addition to its general function as a component of proteins, methionine is specifically required for translation initiation and is crucial for a variety of methyltransferase reactions, both as a precursor of S-Adenosyl-Methionine (SAM).
1. as in E. coli. Full Transsulfuration pathway (has CTGS, CTBL) via O-Succinyl-L-Homoserine (has HSST), and with Methionine Transporter.
2. as in Staphylococcus aureus. Full Transsulfuration pathway via O-Acetyl-L-Homoserine (has HSAT), and with Methionine Transporter.
3. Full Sulfhydrylation pathway (has AHSH) via O-Acetyl-L-Homoserine, and with Methionine Transporter.
4. as in Streptococcus spp. Full Sulfhydrylation pathway via O-Succinyl-L-Homoserine, and with Methionine Transporter.
5. as in Listeria spp. Both Sulfhydrylation and Transsulfuration pathways via O-Acetyl-L-Homoserine, and with Methionine Transporter.
6. as in Clostridium acetobutylicum. Both Sulfhydrylation and Transsulfuration pathways via O- Succinyl -L-Homoserine, and with Methionine Transporter.
7. as in plants. Full Transsulfuration pathway via O- Phospho -L-Homoserine (has HK).
8. as in Enterococcus faecalis. no de novo pathway, with Methionine Transporter
9. unknown pathway
10. as in Bacillus cereus. Both Sulfhydrylation and Transsulfuration pathways via O- Succinyl -L-Homoserine or O-Acetyl-L-Homoserine (has both HSST and HSAT), and with Methionine Transporter.
|Notes||#1 HSDH (hom): Homoserine is derived from aspartate semialdehyde by the homoserine dehydrogenase Hom. In E.coli, the hom domain is fused to aspartate kinase domain and exists in two copies (threonine-regulated ThrA and methionine–regulated MetL)
#2 HSST (metB in B. subtilis or metA in E.coli): Acylation of homoserine is catalyzed by homoserine acetyltransferase MetB in Bacillus subtilis according to (7) and by homoserine succinyltransferase MetA in E. coli, and these two enzymes are homologous.
#3 HSAT (metX): It was shown to be homoserine acetyltransferase and it is not related to HSST
#4 AHSH (metY): O-acetylhomoserine is directly converted to homocysteine by O-acetylhomoserine sulfhydrylase MetY, utilizing sulfide as the sulfur donor (11)
#5 CTGS (metI in B. subtilis or metB in E.coli): MetB from E.coli is homologous to MetB from B. subtilis, but they are not real orthologs (data from analysis of phylogenetic tree, (1))
#6 CTBL (metC in B. subilis and E.coli): MetC from E.coli and B. subtilis are homologous, but they are not real orthologs (data from analysis of phylogenetic tree, (1))
#7 and #8 CTGL (yrhB in B. subilis) and CTBS (yrhA in B. subilis): These two enzymes are present only in some organisms and involved in synthesis of cysteine from homocysteine via the reverse transsulfuration pathway. CTGL has a similarity to CTGS (#5) and CTBL (#6), whereas CTBS is similar to the cysteine synthase CysK.
#9 and #10 MetH and MetE: Two types of methionine synthases are involved in methylation of homocysteine by methyl-THF in bacteria. Reaction catalyzed by coenzyme B12-dependent protein MetH is more than hundred-fold faster than the reaction catalyzed by B12-independent isoenzyme MetE (8). MetH contains four domains: N-terminal homocysteine-binding domain (Homocysteine S-methyltransferase domain), methyl-THF-binding domain, B12-binding domain, and an C-terminal domain involved in reactivation of spontaneously oxidized coenzyme-B12. MetE is not similar to MetH.
#11 BhmT in mammals and a single bacterium (Oceanobacillus): Betaine--homocysteine S-methyltransferase converts betaine and homocysteine to dimethylglycine and methionine, respectively. BhmT is a single-domain protein that is similar to the Homocysteine S-methyltransferase domain of MetH.
#12 MTHFR (MetF in E.coli, or yitJ in B.subtilis): In enterobacteria, the methyl group of methionine is donated by methyl-THF that is formed by reduction of methylene-THF in a reaction catalyzed by MetF. An ortholog of metF in B. subtilis (yitJ) is only weakly similar to metF and has an additional N-terminal homocysteine-binding domain, that is similar to BhmT and to the N-terminal domain of MetH.
#13 MSD (msd in some bacteria): cobalamine activation (or AdoMet-binding) domain of B12-dependent methionine synthase MetH. It was firstly identified from genome context in Thermotoga maritima (TM0269). MetH (TM0268) alone should be capable of performing the main reaction: conversion of homocysteine to methionine using methyl-THF as a methyl donor via cobalamine cofactor. However it would lack the ability of reactivation (as needed to compensate for occasional oxidation of the cofactor). In human and E.coli MetH this function is performed by the C-terminal domain. TM0269, a distant homolog of the missing C-terminal domain, is expected to compensate for this function.
#14, 15, 16 MetNPQ (previously yusABC in B. subtilis): ABC-type transport system specific for methionine. It contains a periplasmic substrate-binding protein, a transmembrane permease and an ATPase protein.
#17 MetT: a single-component secondary methionine transporter in diverse bacterial species, which is predicted from the genome context and regulatory site analysis (1).
#18, #19 SAMS (MetK in E.coli and B. subtilis): S-adenosylmethionine (SAM) is synthesized from methionine and ATP by SAM synthetase. Bacterial-type (MetK) and archaeal-type SAM synthetases are not similar on the sequence level.
#20, #21 SAMM (SAM methyltransferase): SAM is required for a variety methyltransferase reactions in the cell. #20 (yrrT in bacilli) and #21 (so-called ubiG in Clostridia) were predicted by genome context analysis as SAM methyltransferases involved in backward synthesis of cysteine from methionine.
#22, #23, #24 SAHCN, RHMC or AHMC (SAM recycling pathway): Utilization of SAM as a methyl donor results in formation of S-adenosylhomocysteine (SAH), which is then cleaved by SAH nucleosidase encoded by mtn in B. subtilis (or its ortholog, pfs in E.coli) to yield adenine and S-ribosylhomocysteine (SRH). SRH is then cleaved by SRH hydrolase (luxS in E.coli) to yield ribose and homocysteine. A second pathway for direct cleavage of SAH to homocysteine and adenosine by SAH hydrolase, which was found only in some genera (including Mycobacterium and Streptomyces).