A Salmonella typhimurium mutant dependent upon carbamyl aspartate for resistance to 5-fluorouracil is specifically affected in ubiquinone biosynthesis

Abstract

The isolation and properties of a mutant dependent upon exogenous carbamyl aspartate for resistance to 5-fluorouracil are described. The mutant was deficient in the synthesis of ubiquinone and accumulated a quinone provisionally identified as the ubiquinone precursor 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone. The mutation resulted in an alteration in the regulation of synthesis of enzymes involved in de novo pyrimidine biosynthesis but did not establish a functional block in dihydroorotate dehydrogenase activity in vivo. Conditional resistance to 5-fluorouracil apparently occurred through an inhibition of the conversion of the analog to the nucleotide level.