METABOLISM OF MICROORGANISMS •^69 



monly used for this antibiotic, but it is also known by tlie more chemical 

 name chloramphenicol. The compound contains chlorine and is pro- 

 duced by a streptomyces, hence it is quite apparent how the word 

 Chloromycetin came to be devised. The microorganism producing 

 Chloromycetin is called Streptomyces venezuelae, an obviously poor name 

 since it denotes geographical origin and not an inherent characteristic. 

 The microorganism was obtained from a sample of soil from Venezuela. 

 It has also been found in soils from Illinois and Japan and is probably 

 widely distributed in nature. 



It is produced industrially both by fermentation and by synthesis. 

 To date it is the only commercial antibiotic that is produced synthetically 

 as well as by fermentation. 



The most distinctive feature about the chemical structure of Chloro- 

 mycetin is the nitro group. Few organic compounds in nature contain 

 a nitro group. It also contains chlorine, which, though not common, 

 occurs in aureomycin and a number of mold products, e.g., erdin. The 

 presence of an amide linkage relates it to peptides and explains its 

 hydrolysis by enzymes found in cells of Proteus vulgaris. Chloromycetin 

 contains no acidic or basic groups, hence it does not form salts. It is 

 a neutral compound that crystallizes as colorless needles or elongated 

 plates. 



Chloromycetin is relatively inactive against gram-positive bacteria, 

 but is very potent against the gram-negative bacteria associated with 

 intestinal diseases such as typhoid fever and dysentery. It is active 

 against the same rickettsial and viral diseases as aureomycin and terra- 

 mycin. 



Chloromycetin is relatively stable to acids and alkali, is rapidly ab- 

 sorbed from the gastro-intestinal tract, and hence is usually given by 

 mouth. Liver and kidney tissues reduce the — NO2 group to an — NHo 

 group. About 90 per cent of the administered dose is excreted as an 

 inactive compound and 10 per cent as unchanged Chloromycetin in 24 

 hours. 



Terramycin, aureomycin, and Chloromycetin are alike in bacterial spec- 

 trum and appear to be similar in their mode of action; they interfere 

 strongly with protein synthesis but are much less effective in stopping 

 nucleic acid synthesis. A more specific reaction in protein metabolism 

 has been observed for Chloromycetin. It acts as an antagonist against 

 phenylalanine, but the antagonism is noncompetitive. Only low con- 

 centrations of Chloromycetin can be overcome by addition of phenyl- 

 alanine. At higher concentrations its effect cannot be reversed by 

 adding more phenylalanine. This makes Chloromycetin a particularly 

 effective antimetabolite since the inhibited organism cannot counteract 

 the Chloromycetin by producing more phenylalanine. 



Bacitracin, Polymyxin, and Tyrothricin. These three antibiotics are 

 all polypeptides and are produced respectively by Bacillus licheniformis, 



