VI. BTOGENESIS 447 



From our knowledge of the chemical steps that are used in the thiamine 

 synthesis, we may assume that an orjijanism completely autotrophic for 

 thiamine must lie able to elTect the synthesis of the j)yrimidine and thiazole 

 moieties and to condense pyrimidine and thiazole into thiamine. 



Ai)out the pyrimidine sj^ithesis in vivo we are not well informed. There 

 are indications that the thiazole part may be synthesized by the condensa- 

 tion of methionine, acetaldehj'de and ammonia.^- * In this way a-amino-/3- 

 (4-methylthiazole-5) -propionic acid is formed. 



It is known that certain microorganisms can perform transformations 

 analogous to the conversion of this acid to the thizaole part of thiamine.^ 



Bonner and Buchman^ stated that pea roots synthesize thiazole from the 

 precursors thioformamide and chloroacetopropyl alcohol that are used for 

 the in vitro synthesis. When these two precursors of thiazole are given along 

 with the pj^rimidine moiety of thiamine to pea roots, growth is as good as 

 when thiamine is supplied. In the in vitro synthesis chloroacetopropyl alco- 

 hol is essential; the pea roots are able to use also acetopropyl alcohol. 



*" "^""^ , S C— CHa— CH2OH 



HCSXH. + CH3COCnClCH2CH20H ] 1 11 



in vivo jj_^ C— CH3 



\ / 



N 

 Thioformamide chloroacetopropylalcohol Thiazole part of thiamine 



in vitro 



HCSNH2 + CH3COCH2CH2CH2OH I Thiazole part of thiamine 



in vivo 



Acetopropylalcohol 



Wild Neuros-pora strains are able to synthesize thiamine. Tatum in his 

 extensive experiments on mutants of Neurosyora obtained four strains that 

 had lost the ability to synthesize thiamine. Accumulation of a pyrimidine 

 component bj^ mutant 18558 and of both pyrimidine and thiazole compo- 

 nents by 9185 was shown in bioassays. So Tatum and BelF shoAved that 

 the evidence obtained with strains 9185 and 18558 is consistent with the 

 view that the synthesis in Neurospora takes place through the production 

 of the thiazole and pyrimidine moieties, with their subsequent coupling. 



WooUey and White' studied the inhibition of the growth of a number of 

 microorganisms by the antithiamine, pyrithiamine. They found that the 

 inhibition of the gro\Hh of microorganisms by pyrithiamine is related to 

 their requirements for thiamine or its components. They found furthermore, 



« C. R. Harrington and R. C. C. Moggridge, Biochem. J. 34, 685 (1940). 

 ' J. Bonner and E. R. Buchman, Proc. Natl. Acad. Sci. U. S. 24, 431 (1938). 



8 E. L. Tatum and T. T. Bell, Am. J. Botany 33, 15 (1946). 



9 D. W. Woolley and A. G. C. White, /. Exptl. Med. 78, 489 (1943). 



