Regulation of folylpoly-gamma-glutamate synthesis in bacteria: in vivo and in vitro synthesis of pteroylpoly-gamma-glutamates by Lactobacillus casei and Streptococcus faecalis.
Lactobacillus casei and Streptococcus faecalis accumulated labeled folic acid and metabolized this compound to poly-gamma-glutamates of chain lengths of up to 11 and 5, respectively. Octa- and nonaglutamates predominated in L. casei, and tetraglutamates predominated in S. faecalis. The most effective monoglutamate substrates for the L. casei and S. faecalis folylpoly-gamma-glutamate (folylpolyglutamate) synthetases were methylene- and formyltetrahydrofolate, respectively. Methylenetetrahydropteroylpoly-gamma-glutamates were the preferred poly-gamma-glutamate substrates for both enzymes and, in each case, the highest activity was observed with the diglutamate substrate. The final distribution of folylpolyglutamates in these bacteria appeared to reflect the ability of folates with various glutamate chain lengths to act as substrates for the bacterial folylpolyglutamate synthetases. The proportions of individual folylpolyglutamates were markedly affected by culturing the bacteria in medium containing adenine, whereas thymine was without effect. Adenine did not affect the level of folylpolyglutamate synthetase in either organism but caused a large increase in the proportion of intracellular folates containing one-carbon units at the oxidation level of formate, folates which are substrates for enzymes involved in purine biosynthesis. The folates with shorter glutamate chain lengths in bacteria cultured in the presence of adenine resulted from primary regulation of the de novo purine biosynthetic pathway, regulation which caused an accumulation of formyltetrahydropteroyl-poly-gamma-glutamates (folate derivatives that are ineffective substrates for folylpolyglutamate synthetases), and did not result from regulation of folylpolyglutamate synthetase per se.
D000225:Adenine / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000378:metabolism*; D005492:Folic Acid / Q000031:analogs & derivatives*; D005575:Formyltetrahydrofolates / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D011624:Pteroylpolyglutamic Acids / Q000096:biosynthesis* / Q000378:metabolism; D013379:Substrate Specificity; D013763:Tetrahydrofolates / Q000378:metabolism; D013941:Thymine / Q000494:pharmacology
D005575:Formyltetrahydrofolates; D011624:Pteroylpolyglutamic Acids; D013763:Tetrahydrofolates; C024898:methylenetetrahydropteroylpolyglutamate; C013123:5,10-methylenetetrahydrofolic acid; D005492:Folic Acid; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase; D000225:Adenine; D013941:Thymine