Abstract
Why is the solution to increasing the flux in a pathway not simply: (i) find the rate-limiting step; and (ii) amplify or activate it? There are theoretical and experimental grounds for expecting the above approach to fail:
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Control of flux is distributed; rarely does any one enzyme have a large share of this control. This will be illustrated with results for ribulosebisphosphate carboxylase and the control of the reductive pentose phosphate pathway.
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Amplification or activation of a single enzyme will generally yield a limited flux response. Theory predicts this; practical examples include amplification of phosphofructokinase in potato tubers.
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Large flux increases require coordinate changes in several/many enzyme activities — the method used in vivo. Again, this can be predicted theoretically and has been partially demonstrated in the engineering of yeast tryptophan synthesis. The in vivo examples include light activation of photosynthesis.
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Fell, D.A., Thomas, S. (1999). Increasing the flux in a metabolic pathway: a metabolic control analysis perspective. In: Kruger, N.J., Hill, S.A., Ratcliffe, R.G. (eds) Regulation of Primary Metabolic Pathways in Plants. Proceedings of the Phytochemical Society of Europe, vol 42. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4818-4_13
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DOI: https://doi.org/10.1007/978-94-011-4818-4_13
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