Chapter 7 



Biogenesis of Antibiotics 



Only scattered attention has been paid 

 hei-etofoi'e to the mechanism of formation of 

 antil)iotics and to their role in the metabo- 

 lism of the organisms prodiu.-ing these sub- 

 stances. 



In this area, a number of (juestions can be 

 asked which remain, for the most part, un- 

 answered. Are antibiotics essential cell con- 

 stituents? Are they storage products? Are 

 they waste products of microbial metabo- 

 lism? Are they a result of "abnormal" or 

 "shunted" biosynthesis which may be con- 

 trolled by certain special constituents of the 

 medium? What role do they play in the life 

 of the organisms producing them? What 

 effect do they exert upon these organisms? 

 Does the fact that they exert an inhibiting 

 effect upon the growth of other microbes 

 suggest that they play a role in the sur\'ival 

 of the organisms producing them? 



It has long been recogniz(Kl that environ- 

 ment exerts a marked effect upon the com- 

 position of the microbiological population 

 living in a natural or an artificial substrate. 

 Important en\'ir()iun('ntal factors include 

 humidity, aeration, temperature, and pH 

 as well as the nature and concentration of 

 available nutrients. These factors also exert 

 an important influence upon the metabolic 

 processes and even upon the chemical com- 

 position, morphology, and life cycle of the 

 organisms involved. In addition to factors 

 of nutrition and environment, the nature of 

 the microbial p()i)ulati()u also depends upon 

 the presence of other organisms and upon 

 their metabolic products. These exert a 



variety of associative or antagonistic effects 

 upon the various members of the popu- 

 lation. We have already discussed briefly 

 the role of antibiotics in nature, and have 

 concluded that it is doubtful that antibiotics 

 play an important role in microbial ecology 

 (Chapter 1). We will discuss here the part 

 played by antibiotics directly on the cells 

 of the producing organisms rather than in- 

 directly, through their action on other micro- 

 organisms. 



Role of Antibiotics in the Biology of the 

 Producing Organisms 



Let us begin this discussion })y an exami- 

 nation of the effect of various factors upon 

 the concentration of antibiotics produced by 

 certain cultures of actinomycetes. Whether 

 the active substance is excreted into the 

 medium, whether it is liberated from the 

 mycelium when the latter undergoes lysis, or 

 whether it is extracted from the mycelium 

 by means of special organic solvents during 

 the isolation of the antibiotic are other 

 important (luestions that must be con- 

 sidered. 



In the i)i-oduction of actinomycin, for 

 example, every change in tlie composition 

 of the medium and in the cultural conditions 

 brings about not only a change in the yield 

 of the antibiotic, but also in the nature and 

 ratios of its amino acid make-up. The syn- 

 thesis of the mycelium and the yield of 

 actinomycin show the same course. Both 

 reach a maximum at a time of complete 

 consumption of the carbon source; when 



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