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FOLIC ACID DERIVATIVES SYNTHESIZED DURING GROWTH OF DIPLOCOCCUS PNEUMONIAE

Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, and Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University Medical College, New York, New York

ABSTRACT

SIROTNAK, F. M. (Sloan-Kettering Institute for Cancer Research, New York, N.Y.), GLORIA J. DONATI, AND DORRIS J. HUTCHISON. Folic acid derivatives synthesized during growth of Diplococcus pneumoniae. J. Bacteriol. 85:658–665. 1963.—Under cultural conditions permitting synthesis of folic acid in an amount greatly in excess (20- to 30-fold) of that required for maximal growth of Diplococcus pneumoniae, 85 to 90% of the growth factor accumulated as polyglutamates. Approximately equal amounts of mono- and diglutamates made up the remaining 10 to 15% found in culture material. Most of the polyglutamates occurred intracellularly, in a proportion of triglutamates to higher glutamates of about two to one. Only 10 to 15% of all folic acid derivatives (mono-, di-, and polyglutamates) found had folinic acid (5-formylfolate-H₄) activity for Pediococcus cerevisiae. Practically all synthesis of the glutamyl-peptide moieties of folate seems to occur at an enzymatic step prior to folic acid, since no appreciable peptide formation occurred under conditions blocking folate synthesis. Sulfanilamide inhibition of growth by a block in folate synthesis was reversed by the addition of dihydrofolic acid, but not folic acid. The examination of two genetically distinct amethopterin-resistant mutant strains has revealed no gross differences in folate accumulation during growth when compared with the wild strain.