Bacterial variations on the methionine salvage pathway.
BACKGROUND
The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism.


RESULTS
This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase), belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate).


CONCLUSIONS
A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya), with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and RuBisCO, as an enolase, in some Firmicutes). Many are highly dependent on the presence of oxygen, suggesting that the ecological niche may play an important role for the existence and/or metabolic steps of the pathway, even in phylogenetically related bacteria. Further work is needed to uncover the corresponding steps when dioxygen is scarce or absent (this is important to explore the presence of the pathway in Archaea). The thermophile T. tengcongensis, that thrives in the absence of oxygen, appears to possess the pathway. It will be an interesting link to uncover the missing reactions in anaerobic environments.
Sekowska
Agnieszka
A
HKU-Pasteur Research Centre, 8, Sassoon Road, Pokfulam, Hong Kong, SAR Hong Kong. sekowska@pasteur.fr
Dénervaud
Valérie
V
Ashida
Hiroki
H
Michoud
Karine
K
Haas
Dieter
D
Yokota
Akiho
A
Danchin
Antoine
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D001412:Bacillus subtilis / Q000378:metabolism*; D006868:Hydrolysis; D007711:Klebsiella pneumoniae / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D012273:Ribulose-Bisphosphate Carboxylase / Q000378:metabolism; D013872:Thionucleosides / Q000378:metabolism*
D013872:Thionucleosides; C021714:2-methylthioadenosine; D008715:Methionine; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D012273:Ribulose-Bisphosphate Carboxylase; D010751:Phosphopyruvate Hydratase; D000241:Adenosine; D010100:Oxygen