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

DISCUSSION
cells maintain viability by deriving energy from degradation of macromolecules. The
current work provides evidence for the first time of a relation between the genes
involved in biosynthetic and degradation pathways and supercoiling preference of gene
activities. Table 2 illustrates that the biosynthetic pathways are made up predominantly
of Hyp genes while the degradation pathways prefer Rel genes, implicating the
supercoiling as global regulator of metabolic functions. A more detailed analysis of the
gene promoters with respect to their sequence organization, their topological properties,
their preference of sigma factors and any NAP binding can help to better understand the
mechanistic basis of the functional switch from biosynthesis to degradation.
The tricaboxylic acid (TCA) cycle and the glyoxylate bypass provide an
example for coupling of supercoiling sensitivity to metabolic function. The TCA cycle
(Figure 15A) plays two essential roles in metabolism. First, the cycle is responsible for
the total oxidation of acetyl coenzyme A (CoA), derived mainly from the pyruvate
produced by glycolysis. Second, TCA cycle intermediates are required in the
biosynthesis of several amino acids. For long the TCA cycle was considered as
housekeeping pathway, but of lately evidences show that it is an inducible pathway
[Iuchi & lin, 1988; Iuchi et al., 1989; Guest & Russell, 1992]. The full TCA cycle in
E.coli is seen only during aerobic growth on acetate or fatty acid and under anaerobic
conditions the cycle is not used for energy production but used more as a biosynthetic
pathway. The growth on acetate or fatty acids also results in the induction of the
glyoxylate shunt, which is the biosynthetic pathway to replenish the intermediates for
amino acid biosynthesis. The gene icdA which codes for IDH (isocitrate dehydogenase)
plays a key role in partition of carbon between TCA cycle and glyoxylate shunt. The
switch is controlled by phosphorylation of IDH which inactivates IDH and activates the
glyoxylate bypass. The genes in the bypass show preference for hypernegative
supercoiling while the suc and sdh genes of the TCA cycle are more active under
relaxation of DNA. Thus hypernegative supercoiling reflecting increased gyrase activity
resulting from a high ATP/ADP ratio favours the glyoxylate bypass and substrate
synthesis. Activation of the suc and sdh gene operons under conditions of DNA
relaxation (low ATP/ADP ratio) helps in capturing the energy released by carbon
metabolism. The switching gene icdA itself is also sensitive to hypernegative
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