Abstract
NORLEUCINE appears to inhibit bacterial growth due to incorporation into proteins in place of methionine, as the analogue inhibits methionine incorporation but does not significantly reduce its synthesis1. It has been demonstrated2 that resistance to amino-acid analogues in Escherichia coli is achieved frequently by over-synthesis of the amino-acid itself, and this appears to be the case with norleucine-resistant strains as some excrete a substance (presumably methionine) which stimulates the growth of sensitive strains in the presence of the analogue. Colonies of such resistant strains have haloes of growth around them when plated on sensitive strains in the presence of norleucine. A mutant (strain P-76-2) selected as a norleucine-resistant strain by this method had increased amounts of homocysteine methylase (compared to the parent strain P-76) when grown in minimal medium and the formation of the enzyme was only slightly reduced by growth with methionine2,3. It was proposed that strain P-76-2 failed to produce a represser or formed a faulty one. The probable excretion of methionine and the high enzyme-level supported this idea. It was also possible that resistance to norleucine was due to decreased permeability to the analogue; failure of methionine to repress enzyme formation would then be due to a similar permeability restriction. The increased levels of homocysteine methylase on minimal medium are, however, not consistent with this view, and as methionine-requiring auxo-trophs, isolated from strain P-76-2, grow well with small amounts of methionine there seems to be no restriction on the entry of this amino-acid. The control of methionine synthesis in strain P-76-2 has been further investigated to ascertain whether all the enzymes of the methionine-synthesis pathway are de-repressed and also to determine whether methionine exerts a feedback inhibition effect on the activity of the first enzyme as it does in other strains4.
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ROWBURY, R. Resistance to Norleucine and Control of Methionine Synthesis in Escherichia coli. Nature 206, 962–963 (1965). https://doi.org/10.1038/206962a0
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DOI: https://doi.org/10.1038/206962a0
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