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N-methyl-N'-nitro-N-nitrosoguanidine (NH)-induced mutagenesis with subsequent selection for resistance to toxic amino acid analogues (azaserine, m-fluoro-DL-phenylalanine, and 6-diazo-5-oxo-L-norleucine) was applied to Pseudomonas aurantiaca B-162. The resulting strains produced phenazine antibiotics three times more efficiently than the wild type strain and ten times more efficiently than the known pseudomonad strains. Overproduction of phenazine antibiotics was shown to result either from deregulation of 3-deoxi-D-arabinohepulosonate-7-phosphate synthase (DAHP synthase), the key enzyme of the aromatic pathway (removal of inhibition by phenylalanine, tyrosine, and phenazine), or overproduction of N-hexanoyl homoserine lactone, the regulatory molecule of positive control of cellular metabolism (QS system).

The effect of substrate analogues on glutamin-(asparagin-)ase from Pseudomonas aurantiaca-548 has been studied. The enzyme was demonstrated to be highly sensitive to the the action of 6-diazo-5-oxo-L-norleucine and azaserine. L-isomers of glutamine, aspartate, glutamate and several other substrate analogues with free alpha-amino groups protected the enzyme against the inhibitory DON effect. Thus, thorough preliminary selection of appropriate inhibitors, their dosage and treatment duration is needed for the recommendation of combined enzyme-inhibitor application in anti-tumour chemotherapy.