Cytotoxicity of dihydropteroate in Saccharomyces cerevisiae.
Microbes and plants synthesise folate using a unique biosynthetic pathway that is absent in animals. The end product, tetrahydrofolate, is utilised by all forms of life. In this study, an intermediate in this synthesis, dihydropteroic acid, was found to be toxic to Saccharomyces cerevisiae. Further tests were performed on mutants deficient in folate synthesis. One mutant specifically lacked dihydropteroate synthase and the second lacked dihydrofolate synthase. Dihydropteroic acid itself appeared to be toxic since both of these mutants were also inhibited. These results suggest novel ways in which antifolate therapy may be developed.
Bayly
Ann M
AM
CSIRO Health Sciences and Nutrition, 343 Royal Parade, Parkville, Vic., 3052, Australia.
Macreadie
Ian G
IG
D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D005492:Folic Acid / Q000096:biosynthesis / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011622:Pterins / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development
D011622:Pterins; C000978:dihydropteroate; D005492:Folic Acid; D004094:Dihydropteroate Synthase