A new thiamin salvage pathway.
The physiological function for thiaminase II, a thiamin-degrading enzyme, has eluded investigators for more than 50 years. Here, we demonstrate that this enzyme is involved in the regeneration of the thiamin pyrimidine rather than in thiamin degradation, and we identify a new pathway involved in the salvage of base-degraded forms of thiamin. This pathway is widely distributed among bacteria, archaea and eukaryotes. In this pathway, thiamin hydrolysis products such as N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (formylaminopyrimidine; 15) are transported into the cell using the ThiXYZ transport system, deformylated by the ylmB-encoded amidohydrolase and hydrolyzed to 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP; 6)-an intermediate on the de novo thiamin biosynthetic pathway. To our knowledge this is the first example of a thiamin salvage pathway involving thiamin analogs generated by degradation of one of the heterocyclic rings of the cofactor.
Jenkins
Amy Haas
AH
Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, New York 14853, USA.
Schyns
Ghislain
G
Potot
Sébastien
S
Sun
Guangxing
G
Begley
Tadhg P
TP
D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology / Q000379:methods; D005816:Genetic Complementation Test; D006863:Hydrogen-Ion Concentration; D006867:Hydrolases / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D009154:Mutation; D011743:Pyrimidines / Q000737:chemistry; D012987:Soil; D013831:Thiamine / Q000737:chemistry*; D013833:Thiamine Monophosphate / Q000737:chemistry
C101901:4-amino-5-hydroxymethyl-2-methylpyrimidine; D011743:Pyrimidines; D012987:Soil; D013833:Thiamine Monophosphate; D006867:Hydrolases; C022731:thiaminase II; D013831:Thiamine