Regulatory mutants of dihydrofolate reductase in Escherichia coli K12

Summary Trimethoprim inhibits dihydrofolate reductase. Mutations conferring trimethoprim-resistance on E. coli K12 result in either an altered reductase with decreased affinity for the drug, or in 2–30 fold higher levels of the enzyme. Studies of the latter class of mutants indicate that dihydrofolate reductase is regulated by a diffusible molecule, and is probably under negative control. The regulatory mutants, some of which are temperature-sensitive, act cis.