Chapter 4 



Production of Antibiotics 



The problem oi the possible formation of 

 antibiotics in nature has already been dis- 

 cussed in Chapter 1. In the present chapter 

 the methods used for the empirical produc- 

 tion of antibiotics by actinomycetes in vitro 

 are discussed. What is known of the bio- 

 genesis and the mechanism of biosynthesis of 

 antibiotics by these organisms will be con- 

 sidered in Chapter 7. 



The ability to form antibiotics is one of 

 the numerous reactions characteristic of 

 various biological systems. The micro- 

 biologist has learned to recognize and favor 

 such systems. The chemist has developed 

 methods for the isolation of antibiotics. 

 Techniques for their rapid production on a 

 large scale have been developed by the 

 engineer. The pharmacologist and the clini- 

 cian have suggested procedures for their 

 practical evaluation. By combined effort, 

 these investigators have succeeded in ob- 

 taining powerful drugs for combatting a 

 variety of infectious diseases. To appreciate 

 the problems invoh'ed, one must consider 

 the following facts: 



1. Xot all kinds of micn)l)es and not even 

 all strains of a particular group of microbes 

 are able to form antibiotics. This phenome- 

 non is not so widely distributed among the 

 microbes inhabiting our planet as to warrant 

 any generalization in regard to their role in 

 microbial life or in the survival of the or- 

 ganisms capable of forming such antibiotics. 



2. Different strains of a microbe capable 

 of producing a given antibiotic vary greatly, 

 both (iualitati\'ely and (luantitatively, hi this 

 capacity, l^roduction of an antibiotic is not a 



fixed property of the organism and is evi- 

 denced only when the organism is grown in 

 special media and in selected environments. 



3. The ability of a particular microbe to 

 form antibiotics may easily be lost under 

 certain conditions of culture or as a result of 

 mutation. 



4. The concentration of a j^articuiar anti- 

 biotic produced by a given microbe can be 

 greatly increased by strain selection, by 

 de^'elopment of special media, and by im- 

 pro\'ement of conditions of cultix'ation. 



5. The sam(^ oi'ganism may be able to form 

 different anlibiotics in different media and 

 under different conditions of culti\-ation. 

 Each antibiotic is characterized by a given 

 chemical structure and by its antibiotic 

 spectrum. 



6. The same culture may have the capac- 

 ity of forming, in the same medium and at 

 the same time, several antibiotics or various 

 chemical modifications of the same anti- 

 biotic. As many as five to seven different, 

 although chemically related, antil)iotics have 

 been found in the same culture of the same 

 organism. 



7. The same antibiotic, or closely related 

 chemical modifications, can be formed by 

 different organisms. 



Among all groups of mici'oorganisms, the 

 actinomycetes ha\'e proved to be the richest 

 source of antibiotics. Alost of these anti- 

 biotics are produced by members of the 

 genus Streptomyces; only a few of them are 

 produced by strains of Xocardio and M icro- 

 monospora. 



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