The control of sugar utilization by Escherichia coli .

Mutants of Escherichia coli devoid of phosphopyruvate synthase activity (pps-) differ from pps+ organisms in being unable to grow upon C-3 acids, such as pyruvate, as sole carbon sources, although there are no significant differences in their ability to grow on sugars, on acetate, or on utilizable intermediates of the tricarboxylic acid cycle. However, the growth-rate of pps- mutants on glucose, fructose, mannose, mannitol or sorbitol is markedly inhibited by the addition of pyruvate: this inhibition persists until the pyruvate has been utilized, after which the normal growth rates are resumed. Pyruvate does not decrease the growth rate of pps- mutants on ribose, gluconate, glycerol, galactose, maltose, glucose-6- phosphate or fructose-6-phosphate, nor on glucose if C-4 acids are also added. These findings suggest that pyruvate, or some product derived from pyruvate, inhibits the uptake of specific sugars. Several observations indicate that this inhibition is exerted by a product of pyruvate metabolism rather than by pyruvate itself. Growth of double mutants unable to oxidise pyruvate, (pps-, pdh-) or to accumulate pyruvate (pps- usp-) is insensitive to pyruvate; restoration of the pdh+ genotype to pdh- pps- mutants also restores the sensitivity to pyruvate. Growth of mutants unable to form citrate (pps- , cs- ) is very sensitive to pyruvate. These observations imply that the inhibition of hexose utilization is exerted by a product of pyruvate oxidation which is not an intermediate of the TCA-cycle. In accordance with this view, the transport of specific sugars and a sugar analogue into E. coli has been found to be inhibited by pyruvate. It is therefore proposed that acetyl-CoA (or a metabolite close to acetyl-CoA) exerts a feed-back control over the utilization of certain sugars by controlling their entry into the cell. This control is manifested as an inhibition of growth in pps- -mutants which cannot effect the net formation of phospho-pyruvate from pyruvate.