Pfizer Handbook of Microbial Metabolites 422 



Cycloserine (oxamycin) appears to be a cyclized D-ser- 

 ine amide or hydroxamide. As mentioned elsewhere it 

 is known to inhibit the incorporation of D-alanyl-D-alanine 

 into the cell walls of certain bacteria. 



Thiamine is an enzyme prosthetic group of fundamen- 

 tal importance, probably occurring in all living things. 

 Many microorganisms are capable of de novo synthesis, 

 although the vitamin is required in mammalian diets. 

 Some microorganisms incapable of total synthesis can 

 couple certain pyrimidine and thiazole precursors, others 

 require only one of the heterocycles preformed, and cer- 

 tain yeasts have a requirement for thiamine itself. 



Beyond this little is known about the biosynthesis of 

 thiamine. Other naturally occurring thiazoles (e.g. those 

 in certain antibiotics) are known to be derivatives of 

 cysteine. Nakayama has proposed the general scheme :^° 



Cysteine -^ Thiazolidine-4-carboxylic Acid — > 4-Methylthiazoie — > 



4-Methyl-5-(2-hydroxyethyl)-thiazole 



on the basis of work with mutants. Some work has been 

 done on the biosynthesis of other pyrimidines, but appar- 

 ently little on the thiamine constituent. 



Bacillus subtilis incorporates formate C^* extensively 

 into the pyrimidine, but not the thiazole moiety of thia- 

 mines^ In this bacterium the pyrimidine moiety of thia- 

 mine restores growth and formate incorporation into 

 purines and thymine in amethopterin treated cultures. 

 The thiazole part restores thiamine synthesis, but does 

 not show the additional effects. 



It appears now that all enzymes in which thiamine is 

 the active site have the function of decarboxylating a-ke- 

 toacids and of cleaving a-diketones or a-hydroxyketones. 

 These functions were illustrated in an earlier section. 



Thiamine, unphosphorylated and detached from its 

 apoenzyme, is capable of carrying out some of its coen- 

 zyme functions in vitro under favorable conditions. ^-^ ^^' ^^ 



"Hideo Nakayama, Vitamins (Japan) 11 20, 169 (1956). 



SI Martin J. Pine and Robert Guthrie, J. Bacterial. 78 545 (1959). 



s- Shunzi Mizuhara and Philip Handler, /. Am. Chem. Soc. 76 571 

 (1954). 



" Emeteria Yatco-Manzo, Frances Roddy, Ralph G. Yount and 

 David E. Metzler, /. Biol. Chem. 234 733 (1959). 



"Ralph G. Yount and David E. Metzler, ibid. 234 738 (1959). 



