THE VITAMINS B 12 343 



(306) and replaces pteroylglutamic acid for strains of Streptococcus lac- 

 tis (265). Presumably it and the factor active for L. casei are both 

 utilized by the fungi producing them in the same biological reactions 

 for which the coenzyme form of pteroylglutamic acid is required in 

 bacteria and animals. 



14. THE VITAMINS B 12 



The vitamins B 12 comprise a family of compounds, the chemical 

 and biological relationships of which are not fully understood. Vita- 

 min B 12 itself, or cyanocobalamin, was the first discovered, and its 

 structure is now known (22, 110); other cobalamins, e.g., hydroxoco- 

 balamin, can be converted to it by cyanide treatment. A second group 

 of compounds differs from the cobalamins in the nucleotide moiety; 

 these are active for some microorganisms only (25, 62). Vitamin B I2 

 is believed to function in the cell in the synthesis of 1 -carbon fragments, 

 especially the labile methyl group (25). 



Vitamin B 12 and related compounds are required by several bacteria 

 and algal flagellates (62), not, so far as is now known, by actinomycetes 

 or fungi. Higher animals require the vitamin, green plants do not. 



The synthesis of cobalamins occurs in certain of the true bacteria 

 and especially in species of Streptomyces and Nocardia, of the Actino- 

 mycetales (32, 43, 53, 94, 1 16, 203, 209, 232, 267, 305). Commercial sup- 

 plies of the vitamin can in fact be obtained as byproducts of antibiotic 

 production by Streptomyces spp. (324). Cobalt added to the culture 

 medium increases the yield of cyanocobalamin from Streptomyces 

 griseus (104). 



In addition to cyanocobalamin, species of Streptomyces form hy- 

 droxocobalamin (vitamin B 12a , B 12b ), in which the cyanide of cyanoco- 

 balamin is replaced by hydroxyl, and vitamin B 12c , containing a 

 nitrite radical in place of cyanide; all three forms have been isolated 

 from one species, 5. griseus (43). 



Synthesis of vitamin B 12 in the filamentous fungi has not been demon- 

 strated conclusively. Substances active for Lactobacillus leichmanii 

 are formed by Ashbya gossypii (258) and Aspergillus niger (179). How- 

 ever, the L. leichmanii assay is not specific enough to support a final 

 identification (62). 



It has been mentioned earlier that inhibition studies point to 1,2- 

 dimethyl-4,5-diaminobenzene as a precursor of riboflavin. These in- 

 vestigations (310, 311) implicate this compound also as a precursor of 

 the cobalamins; the structure is known to be part of the larger co- 

 balamin molecule. Other evidence bears out the suggestion that the 



