562 BIOTIN 



Thus, oxybiotin, although not a natural product, may replace biotin in 

 metabolic reactions, and the sulfur atom is not essential for biological 

 activity. 



2. Desthiobiotin 



This sulfur-free analog of biotin is just as active in the biotin assay with 

 Saccharomyces cerevisiae as (+)-biotin, and the dose-response curves were 

 essentially identical.^" In contrast, desthiobiotin not only was inactive 

 for Lactobacillus casei but inhibited competitively the response of the 

 organism to biotin. i^^- ^^^ 



Table III contains the available data for the growth-promoting activi- 

 ties of desthiobiotin and other analogs of biotin and oxybiotin. ^^^ 



It appears that organisms which utilize desthiobiotin may convert it 

 into substances which possess biotin-like activity for organisms which re- 

 quire biotin but are unable to utilize desthiobiotin.^^^- ^^®' ^*^ The biotin 

 activity of cells of Saccharomyces cerevisiae grown on either biotin or desthio- 

 biotin may be destroyed with permanganate^'* or with Raney nickel for 

 Lactobacillus casei, L. arabinosus, and Rhizobium trifolii. Thus, it may not 

 be related to oxybiotin. On the other hand, the biotin activity of the com- 

 pound extracted from *S. cerevisiae grown in the presence of desthiobiotin 

 for L. casei indicates that it is due to biotin itself. 



Desthiobiotin had the same activity as biotin for Neurospora crassa, 

 Escherichia coli 58, and Penicillium notatum 21464, but was inactive for an 

 x-ray induced biotin-less mutant of P. chrysogeniim 62078. ^^^ This last 

 organism apparently synthesizes and accumulates desthiobiotin, and the 

 addition of pimelic acid enhanced its intracellular production. 



From these observations it may be concluded that desthiobiotin, in con- 

 trast to oxybiotin, is a normal precursor or is converted to a normal pre- 

 cursor of biotin by a number of organisms. 



Among the other biotin analogs the methyl ester of biotin is inactive 

 for Lactobacillus casei but fully active for yeast. ^ 



Biotin sulfone stimulates the growth of yeast, but even with large 



136 K. Dittmer, D. B. Melville, and V. du Vigneaud, Science 99, 203 (1944). 



1" V. G. Lilly and L. H. Leonian, Science 99, 205 (1944). 



"8 S. H. Rubin, L. Drekter, and E. H. Moyer, Proc. Soc. Exptl. Biol. Med. 58, 352 



(1945). 

 "9 G. M. Shull, B. L. Hatchings, and W. H. Peterson, /. Biol. Chem. 142, 913 (1942). 

 i« V. du Vigneaud, Chem. Eng. News 23, 620 (1945). 

 1" K. Dittmer, V. du Vigneaud, P. Gyorgy, and C. S. Rose, Arch. Biochem. 4, 229 



(1944). 

 i« G. B. Brown and V. du Vigneaud, J. Biol. Chem. 163, 761 (1946). 

 1" E. L. Tatum, /. Biol. Chem. 160, 455 (1945). 

 »" J. A. Hijner, Experientia 2, 312 (1946). 

 1" L. H. Leonian and V. G. Lilly, /. Bacterial. 49, 291 (1945). 



