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Coordinated regulation of gene expression by E ... - Jacobs University

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RESULTS<br />

phosphorylation, are associated with DNA relaxation. In contrast, the glyoxylate<br />

<strong>by</strong>pass, which is predominantly utilized in aerobically growing cultures where most <strong>of</strong><br />

the energy is derived <strong>by</strong> glycolysis is activated <strong>by</strong> negative superhelicity (Figure 15 A<br />

and Table 3). This suggests that high ATP/ADP ratios favouring supercoiling <strong>of</strong> DNA<br />

<strong>by</strong> gyrase would facilitate glyoxylate <strong>by</strong>pass and plastic substrate synthesis, whereas<br />

DNA relaxation would favour the production <strong>of</strong> ATP required to maintain gyrase<br />

activity. Furthermore we found that the de novo pathway <strong>of</strong> nucleotide biosynthesis<br />

explicitly involves the Hyp <strong>gene</strong>s (Figure 15 B). Purine nucleotides are required during<br />

fast growth and the dependence <strong>of</strong> this pathway on supercoiling levels is in keeping<br />

with the prevailing conditions during fast growth. The data presented here thus shows<br />

that supercoiling has a role not only in <strong>regulation</strong> <strong>of</strong> important individual <strong>gene</strong>s but also<br />

in coordinating the activity <strong>of</strong> metabolic pathways.<br />

46

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