]84 CARBON METABOLISM III 



plexing agents, e.g., thiourea (468), which are known to interfere with 

 iodination of tyrosine in the thyroid (551); presumably, the chlorina- 

 tion step requires copper. 



8. PENICILLIN 



The discovery by Fleming (197) of an organism producing penicil- 

 lin initiated a new field of medical and biological investigation, 

 the study of the formation and clinical use of antibiotics. The history 

 of the exploitation of Fleming's discovery has been told elsewhere (1); 

 in general, although extensive application of our knowledge of fungal 

 physiology was essential to the development of methods of production, 

 the physiological studies were less dramatic than the genetic, and few 

 new principles of physiology or biochemistry have emerged from the 

 work on penicillin and other antibiotics. 



The penicillins are produced by several different fungi, including 

 Penicillium spp., Aspergillus spp., and a thermophilic organism tenta- 

 tively identified as Malbranchea pulchella (441). Strains of the Peni- 

 cillium chrysogenum series, including P. notatum, are the most active, 

 and supply the penicillin of commerce. 



The penicillins are alike in their basic chemical structure, but 

 differ in the side chain (R in the formula): 



S 

 / \ /CH 3 

 R— CO— NH— CH— CH C< 



I I I X CH 3 



CO— N CH— COOH 



The natural penicillins whose structures have been determined in- 

 clude: 



1. 2-Pentenylpenicillin (penicillin I, penicillin F) 



2. Benzylpenicillin (penicillin II, penicillin G) 



3. p-Hydroxybenzylpenicillin (penicillin III, penicillin X) 



4. n-Amylpenicillin (dihydro penicillin F) 



5. w-Heptylpenicillin (penicillin IV, penicillin K) 



6. 4-Amino-4-carboxy-w-butylpenicillin (cephalosporin N) (393). 



It is likely that other penicillins formed only in small amounts have 

 not been identified. Benzylpenicillin, now available in crystalline 

 form, is the penicillin of medical practice. 



Extensive information on the metabolism of penicillin-producing 

 fungi, reviewed by Chain (115) and Perlman (417), is available, but 

 it must be said that there is no correlation of any other metabolic 



