nelson: screening methods in microbiology 317 



ants resistant to related antibiotics. Mutants resistant to amino acid 

 analogs have been found to excrete small quantities of the homolo- 

 gous amino acid due to a lack of repression of enzyme synthesis 

 (1, 31, 32). Assuming that similar enzyme repression mechanisms 

 control antibiotic synthesis, it should be possible to select variants 

 lacking suppression, and therefore yielding more antibiotic. The 

 problem of producing analogs of antibiotics is solved for those anti- 

 biotics existing in families, such as the inositol amines streptomycin, 

 neomycin, kanamycin, paromomycin, and the hygromycins, and the 

 macrolide family. Streptomycin- and hygromycin-producing actino- 

 mycetes were found to be sensitive to other inositol amine antibiotics 

 and resistant variants easily obtained on gradient plates, but no 

 increase in production occurred. Erythromycin-producing actino- 

 mycetes proved to be resistant to other macrolides so that no test was 

 possible. 



A general repressor effect of excess glucose on synthesis of 

 enzymes in bacteria may explain the delay in antibiotic synthesis 

 that occurs until growth is nearly complete (34). Occasional increases 

 in antibiotic yield have been obtained by feeding carbohydrate slow- 

 ly, maintaining the measurable external level low. However, the 

 effect of sugar feeds may be due to better pH stabilization rather than 

 to absence of glucose repression. Mutants of bacteria have been found 

 that are not suppressed by glucose (46, 78, 82). Similar variants have 

 not been described in actinomycetes. No increases in yield were found 

 by substituting carbon sources that do not produce glucose on 

 hydrolysis, however. 



A recently described group of mutants lacks permease activity 

 for inorganic ions (76) or amino acids (77, 92). It is difficult to devise 

 a method increasing antibiotic synthesis by interfering with the 

 utilization of amino acids, the principal nitrogenous components of 

 fermentor media. An inability to concentrate phosphate ion might 

 shift metabolism to antibiotic synthesis earlier with a subsequent 

 yield improvement (39, 61). The ability of certain Penicillia strains 

 to accumulate sulfate favors penicillin synthesis (105). "Boostable 

 enzymes" have been described, but restricted growth is necessary for 

 their occurrence (5, 55, 103). 



Variants resistant to actinophages as well as the phage are readily 

 obtained. Various results have been obtained with phage resistant 



