Identification and characterization of an operon in Salmonella typhimurium involved in thiamine biosynthesis

Thiamine pyrophosphate (TPP) is synthesized de novo in Salmonella typhimurium and is a required cofactor for many enzymes in the cell. Five kinase activities have been implicated in TPP synthesis, which involves joining a 4-methyl-5-(beta-hydroxyethyl)thiazole (THZ) moiety and a 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) moiety. We report here identification of a 2-gene operon involved in thiamine biosynthesis and present evidence that the genes in this operon, thiMD, encode two previously identified kinases, THZ kinase and HMP phosphate (HMP-P) kinase, respectively. We further show that this operon belongs to the growing class of genes involved in TPP synthesis that are transcriptionally regulated by TPP. Our data are consistent with ThiM being a salvage enzyme and ThiD being a biosynthetic enzyme involved in TPP synthesis, as previously suggested.