Summary: The possibility of increasing the penicillin production of by feeding lysine at low concentrations to lysine auxotrophs in which the lysine pathways are blocked after α-aminoadipate has been investigated. Three such auxotrophs, strains H, 13a and 45, were isolated after ultraviolet light treatment and characterized. Only one of these mutants (strain H) could be induced to produce penicillin at a rate comparable to that of the parent strain; the others produced much smaller amounts. Chemostat continuous-flow culture of the parent strain and mutant strain H on increasing concentrations of lysine was undertaken. Microbiological assay of the lysine in the chemostat showed that it was completely utilized by both the parent strain and strain H, even when fed at several times the amount required for growth. In the parent strain, the slowly fell from a level of 2·94 u/mg dry biomass/h at zero lysine feed concentrations to 0·45 u/mg dry biomass/h with lysine amounts up to 400 mg/1 in the feed medium. When the mutant strain was grown under similar conditions, penicillin production was stimulated as lysine feed concentrations increased until at 180% excess over that required for growth, a of 2·64 u/mg dry biomass/h was reached, after which the fell at a rate similar to that of the parent strain. At zero growth rate, α-aminoadipic acid stimulated penicillin production, more so when fed continuously to the cultures than when it was added in a single dose. Thus it was found that when lysine was growth-limiting for the auxotroph, and consequently present at minimal concentrations in the mould, penicillin synthesis was inhibited rather than stimulated.


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