Evidence That Bacteriophage-induced Dihydrofolate Reductase Is a Viral Gene Product

Cultures of Escherichia coli infected with bacteriophages T2, T4, T5, or T6 have previously been shown to synthesize relatively large quantities of a dihydrofolate reductase which can be distinguished from the corresponding enzyme found in uninfected cells. Two lines of evidence support the idea that this new enzyme is the specific product of a viral gene. (a) The enzyme has been partially purified from cultures of E. coli B infected with phages T2, T4, T5, and T6 and the properties of the four preparations have been compared. Although the preparations are virtually identical with respect to pH optimum, pyridine nucleotide specificity, sedimentation coefficient, and sensitivity to the inhibitor trimethoprim, significant differences are observed in catalytic efficiency, stability to heat and to urea, and inhibition by aminopterin. (b) A mutant of T4 has been isolated which is unable to direct the formation of dihydrofolate reductase in infected cells. The phage-induced dihydrofolate reductase system presents several advantages, which are discussed in this paper, for comparative studies of enzyme structure and function within a closely related series of proteins.