Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis.
The biosynthesis of thiamin pyrophosphate in eukaryotes is different from the prokaryotic biosynthesis and is poorly understood to date. Only one thiazole biosynthetic gene has been identified (Thi4 in Saccharomyces cerevisiae). Here we report the identification and characterization of a Thi4-bound metabolite that consists of the ADP adduct of 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid. The unexpected structure of this compound yields the first insights into the mechanism of thiamin thiazole biosynthesis in eukaryotes.
Chatterjee
Abhishek
A
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Jurgenson
Christopher T
CT
Schroeder
Frank C
FC
Ealick
Steven E
SE
Begley
Tadhg P
TP
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D005057:Eukaryotic Cells / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013831:Thiamine / Q000096:biosynthesis*; D013835:Thiamine Pyrophosphate / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C089358:THI4 protein, S cerevisiae; D013844:Thiazoles; D009243:NAD; D013835:Thiamine Pyrophosphate; D013831:Thiamine