BIOTIN 551 



thiophene ring. The resulting product, ( + ) desthiobiotin, gave an un- 

 usual result in the biotin assay with Saccharomyces cerevisiae.* 1 ( + ) 

 Desthiobiotin was just as active as ( + ) biotin, and the dose-response 

 curves of the assays were essentially identical. However, the derivative 

 not only was inactive for Lactobacillus casei but inhibited competitively 

 the response of the organism to biotin. 42, 51 



The activity of desthiobiotin is limited to only one of the four optically 

 active forms of the compound. Synthetic DL-desthioallobiotin is inactive 

 for Saccharomyces cerevisiaef synthetic DL-desthiobiotin is approx- 

 imately half as active as ( + ) desthiobiotin. 43,44 



As indicated in Table 13, the utilization of desthiobiotin in place of 

 biotin is rather widespread. Organisms which utilize desthiobiotin have 

 been found to convert the compound into substances which possess 

 biotin-like activity for organisms which require biotin, but do not utilize 

 desthiobiotin. 14, 42, 63 The biotin content of cells of Saccharomyces cerevi- 

 siae grown on desthiobiotin was determined by differential assay with 

 Lactobacillus casei and the yeast. When present in low concentration, the 

 desthio compound was apparently converted quantitatively into biotin; 

 however, at higher concentrations it was less effectively converted into 

 biotin, and resting cells did not convert any measurable amounts of the 

 compound to biotin or biotin-like substances. 14, 42 Further evidence for 

 the conversion of desthiobiotin to biotin is afforded by the observation 

 that for Lactobacillus casei, Lactobacillus arabinosus and Rhizobium 

 trifolii, Raney's nickel destroys the biotin activity of cells of Saccha- 

 romyces cerevisiae grown on either biotin or desthiobiotin. 14 Perman- 

 ganate also destroys the activity. 36 This contrasts with the results obtained 

 with oxybiotin. 



The natural occurrence of desthiobiotin is suggested by the accumula- 

 tion in an x-ray induced biotinless mutant of Penicillium chrysogenum, 

 strain 62078, of a substance which has the biological properties of 

 desthiobiotin. The substance is inactive for Lactobacillus casei, but active 

 for Neurospora crassa and Escherichia coli 58, a mutant strain requiring 

 biotin. 54 The last two organisms utilize either desthiobiotin or biotin 

 while the Penicillium mutant requires biotin and is unable to utilize 

 desthiobiotin. Escherichia coli accumulates a biotin precursor which may 

 be desthiobiotin. 62 



From these observations it appears that desthiobiotin is a normal 

 precursor, or is converted to a normal precursor of biotin by a number of 

 organisms. These results are further substantiated by results with a 

 desthiobiotin inhibitor (p. 468). 



Pimelic acid, which was shown to be an essential growth factor for 

 certain strains of diphtheria bacillus, 56 can be replaced by biotin in the 



