BacferJal Mefabolhm 79 



As an example of the changing concepts of the chemistry 

 of bacterial fermentations, I can tell you something about 

 the formation of butyric acid. Early work on the origin 

 of butyrate indicated that it is formed from a two-carbon 

 compound usually derived from pyruvate. The identity 

 of the two-carbon compound was long a matter of specula- 

 tion. Acetaldehyde was suggested as a possibility. Several 

 persons proposed that acetaldehyde might undergo an 

 aldol condensation to give acetaldol, which might re- 

 arrange to yield butyric acid. But no convincing evidence 

 could be obtained for this theory. Then in 1943, Koepsell 

 and Johnson found that extracts of Clostridium butylicum 

 convert pyruvate to acetyl phosphate rather than to acetal- 

 dehyde. This suggested that acetyl phosphate, a very re- 

 active compound first discovered by Lipmann, might be 

 the two-carbon precursor of butyrate. Support for this 

 idea was obtained by Stadtman (23), who showed that 

 cell-free extracts of Clostridium kluyveri convert acetyl 

 phosphate and acetate more or less quantitatively to buty- 

 rate in the presence of a suitable reducing agent. Later 

 work based on the discovery of coenzyme A by Lipmann, 

 and of acetyl CoA by Lynen, has shown that acetyl CoA 

 rather than acetyl phosphate is the immediate precursor of 

 the four carbon derivatives that are ultimately converted 

 to butyrate. 



The reactions now known to be involved in the con- 

 version of ethanol and acetate to butyrate by C. kluyveri 

 are shown in Figure 7. The ethanol is oxidized to acetal- 

 dehyde and then to acetyl CoA. The carbohydrate-ferment- 

 ing Clostridia do not use ethanol or acetaldehyde, but form 

 acetyl CoA directly from pyruvate. Two molecules of acetyl 

 CoA are then condensed to acetoacetyl CoA which is con- 

 verted by two reduction steps and a dehydration step to 

 butyryl CoA. The latter reacts with acetate to give butyrate 

 and at the same time regenerates a molecule of acetyl 

 CoA, which again enters the cycle. 



