Microbiological Activity of Synthetic Biotin, Its Optical Isomers, and Related Compounds

In a previous report, synthetic and natural biotin were stated to have identical growth-promoting properties for Lactobacillus arabinosus 17-5 (1). This paper gives a more detailed comparison of these substances in the growth of four other biotin-requiring microorganisms. The activities of synthetic dland I-biotin, dl-allobiotin, dl-diamino acid sulfate, desthiobiotin,’ and the probable biological transformation of the latter to biotin are also presented. During the writing of the present paper, data appeared in print on the conversion of desthiobiotin to biotin by yeast (3) and on the ability of the former to replace biotin in the nutrition of various microorganisms (4). Results reported here confirm and extend those already published. The organisms used included three bacteria, Lactobacillus casei (5), Lactobacillus arabinosus 17-5 (6), and Rhixobium trifolii 209 (7) ; a yea.&, Xaccharomyces cerevisiae F6.4 (8) ; and a fungus, Neurospora sitophila 299 (9). Several other yeasts were also tested for their ability t.o grow with desthiobiotin. The media and procedures were, with slight modifications, those described in the literature cited. Synthetic biotin was as potent as the natural vitamin for Lactobacillus casei and Lactobacillus arabinosus (Table I). dl-Biotin was only 50 per cent active, which would be expected if the 1 isomer were inert. However, I-biotin when used in large amounts supported full growth of both bacteria. This is probably due to incomplete separation from the active form, since its potency varied with different crystalline preparations. Contamination with traces of dl-biotin may also explain the small degree of activity of dl-allobiotin. Semiquantitative experiments with Rhizobium trifolii, Saccharomyces cerevisiae, and Neurospora sitophila gave results similar to those obtained with the lactobacilli. Synthetic biotin, like the natural product, combined readily with avidin and could be liberated from the latter by heat. Heating biotin with alkali, under the proper conditions, splits the urea