Some media components which are required for product formation may interfere with the growth of the organism and, therefore, it may be desirable to select for strains which are resistant to the medium component. Polya and Nyiri (1966) applied this approach to the isolation of mutants of P. chrysogenum resistant to phenylacetic acid, a precursor of penicillin and toxic to the organism at high concentrations. Barrios-Gonzalez et al. (1993) used a very similar approach in isolating superior penicillin producers. Alikhanian et al. (1959) selected strains of the oxytetracycline producer, S. rimosus, resistant to high levels of phosphate which prevents product synthesis. This enabled the strain to be used in media containing high levels of corn steep liquor (which is rich in phosphate).
Analogues of repressing media components have been used to select resistant mutants. For example, arsenate and vanadate have been used to isolate phosphate resistant strains (DeWitt et al., 1989) and de-oxyglucose to isolate glucose catabolite repression resistant strains.
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