title: Thiamin (vitamin B1) biosynthesis and regulation: a rich source of antimicrobial drug targets?
abstract: Drug resistance of pathogens has necessitated the identification of novel targets for antibiotics. Thiamin (vitamin B1) is an essential cofactor for all organisms in its active form thiamin diphosphate (ThDP). Therefore, its metabolic pathways might be one largely untapped source of antibiotics targets. This review describes bacterial thiamin biosynthetic, salvage, and transport pathways. Essential thiamin synthetic enzymes such as Dxs and ThiE are proposed as promising drug targets. The regulation mechanism of thiamin biosynthesis by ThDP riboswitch is also discussed. As drug targets of existing antimicrobial compound pyrithiamin, the ThDP riboswitch might serves as alternative targets for more antibiotics.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Enviroment and Bio-Resource of Three Gorges Area, School of Life Sciences, Southwest University, Beibei Chongqing, 400715, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Du
authors.forename: Honghai
authors.initials: H
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D058928:Riboswitch / Q000187:drug effects / Q000502:physiology; D013831:Thiamine / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D058928:Riboswitch; D000095:Acetolactate Synthase; D013831:Thiamine