334 VITAMIN RF.QUIRK M K NTS 



O 



I! 

 • / c \ 



HN NH 



I I 



HC CH 



I i 



H 2 C CH— (CH 2 ) 4 — COOH 



" V 



i 



o 



Biotin sulfoxide 



Tatum (276) studied the nutrition of biotinless mutants of Penicil- 

 lium chrysogenum. One mutant can use desthiobiotin as well as bi- 

 otin; a second mutant accumulates desthiobiotin but cannot use it. 

 Production of desthiobiotin in this strain is increased by provision of 

 pimelic acid [HOOC— (CH 2 ) 5 — COOH]. Equation 3 therefore summa- 

 rizes the known steps in biosynthesis: 



Pimelic acid — » desthiobiotin — » biotin (3) 



Biotin-deficient fungi isolated from nature fall into two groups. The 

 first, exemplified by Ceratostomella ips, Neurospora crassa, Blastomy- 

 ces derma titidis, and yeast (49, 95, 143), can grow, at least to a degree, 

 with desthiobiotin in place of biotin; these fungi are presumably 

 blocked in a step prior to desthiobiotin synthesis. The second group, 

 which includes Ceratostomella pint and Sordaria fimicola, cannot use 

 desthiobiotin (135, 143) and is therefore blocked in the conversion of 

 desthiobiotin to biotin. Those fungi known only to be unable to use 

 pimelic acid in place of biotin (219) cannot yet be placed in either 

 group. We have noted earlier the different responses of spores and 

 pregrown cultures of Memnoniella echinata to desthiobiotin. 



Biotin sulfoxide is formed by Aspergillus niger in synthetic medium; 

 since pimelic acid and desthiobiotin increase the yield, and since added 

 biotin is quantitatively converted to the sulfoxide, it is concluded that 

 A. niger synthesizes biotin as in Equation 3 and then transforms it to 

 biotin sulfoxide (54, 317, 320, 321, 322). Biotin sulfoxide is as active 

 as biotin for Neurospora crassa but not for yeast or the bacteria so far 

 tested (321). Aspergillus niger utilizes azelaic acid also in biotin syn- 

 thesis (318). 



Biocytin, e-N-biotinyl-L-lysine, a naturally occurring form of biotin, 

 is as active as biotin for Neurospora crassa and for a biotin-requiring 

 mutant of Penicillium chrysogenum (319). The oxygen analogue of 



