c II A p T i: n 



I .1 



Production of Antibiotics 



Isolation of Antibiotic-producing Cul- 

 tures 



The actinoniycetcs occupy a leading place 

 among the antibiotic-producing groups of 

 microorganisms. Already, they have yielded 

 nearly 500 compounds and preparations, in- 

 cluding some of the most important chemo- 

 therapeutic agents now known. Some of 

 these antibiotics are active only on bac- 

 teria, others only on fungi; some are active 

 on viruses and phages, and others are ac- 

 tive on tumors. Some of the antibiotics are 

 said to be of a broad spectrum type, able to 

 repress the growth of both bacteria and 

 fungi, or of bacteria, rickettsiae, and the 

 larger viruses. Some have a narrow antibi- 

 otic spectrum, such as those that are largely 

 active against gram-positive bacteria or my- 

 cobacteria, or yeast-like organisms (Waks- 

 nian, 1955). 



Among the antibiotic-producing actino- 

 mycetes, the genus Streptomyces occupies a 

 leading place. Certain groups of this genus, 

 like S. griseus and *S'. lavendulae, are char- 

 acterized by the formation of a large number 

 of different antibiotics. Some antibiotics or 

 closely related groups of antibiotics (anti- 

 biotic complexes) are produced by different 

 organisms. This is true, for example, of the 

 streptomycin and neomycin complexes. 

 There are also marked quantitative vari- 

 ations in the production of antibiotics by 

 different strains of the same organism. Com- 

 position of medium and environmental con- 



ditions play an impoi'tant part in this con- 

 nection. 



A numl)er of the antil)iotics produced by 

 actinomycetes ha\-e l)een isolatcnl in a pure 

 state, their chemical structun-s esta])lished, 

 and their antimicrobial propei'ties studied in 

 detail. Other antil)i<)tics have been described 

 only as preparations, or in such a preliminary 

 manner that it is not certain whether one is 

 dealing with a single entity or with a group 

 of closely related chemical compounds. Only 

 one of the actinomycete antibiotics, chloram- 

 phenicol, has been synthesized. Others have 

 been modified chemically to give compounds 

 with slightly different types of activity. This 

 is true of the formation of dihydrostreptomy- 

 cin from streptomycin and of tetracycline 

 from chlortetracycline. Definite chemical 

 structures have been established for a num- 

 ber of antibiotics, notably the streptomycins, 

 cycloheximide, the actinomycins, the tetra- 

 cyclines, cycloserine, azoserine, erythromy- 

 cins, and sarkomycin. These were found to 

 comprise a \'ariety of highly interesting or- 

 ganic structures, some of which have never 

 been known before. 



Principles of Antibiotic Production 



Certain general principles concerning the 

 production of antibiotics by actinomycetes 

 have been established : 



1. Different strains of an antibiotic-pro- 

 ducing species may form several antibiotics 

 that are not related chemically: S. griseus 



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