The effect of riboflavin analogues upon the utilization of riboflavin and flavin adenine dinucleotide by Lactobacillus casei.

Since new analogues of riboflavin have been synthesized which inhibit the growth of rats and of microorganisms which require riboflavin (l-3), it was decided to test the effect of some of these compounds upon the utilization of riboflavin and flavin adenine dinucleotide (FAD) for growth of Lactobacillus casei. Other compounds structurally related to riboflavin were also studied. It has been shown that isoriboflavin, 5,6-dimethyl-9-(d-l’-ribityl)isoalloxazine, which inhibits the growth of rats on diets free of or low in riboflavin (3), has less than 0.5 per cent of the activity of riboflavin for Lactobacillus casei and has no effect upon acid production by this organism in the presence of maximal amounts of riboflavin (4). The present experiments show that isoriboflavin markedly stimulates acid production by Lactobacillus easei in the presence of suboptimal levels of riboflavin or FAD. Snell and Strong (5) observed similar effects of other riboflavin analogues on the growth of lactic acid bacteria. The ribitylamino compound, 1-ribityl-2-amino-4,5-dimethylbenzene, also has slight riboflavin-like activity and an augmenting effect upon the utilization of riboflavin. However, the addition of alloxan (which can be condensed synthetically with the ribitylamino compound to form riboflavin (6)) permits better utilization of the ribitylamino compound and suggests some synthesis of riboflavin by the bacteria. The diaminophenazine compound (2,4-diamino-7, S-dimethyl-lo-ribityl-. 5, lo-dihydrophenazine), synthesized by Woolley, competitively inhibits the utilization of riboflavin for growth of Lactobacillus casei, as was reported (2) and has the same effect upon the use of FAD. Lumiflavin, 6,7 :9-trimethylisoalloxazine, has both an inhibitory and a stimulatory action upon the growth of Lactobacillus casei. In the presence of relatively large amounts of lumiflavin the growth with riboflavin is