Abstract
Following its original formulation in 1973 (Heinrich & Rapoport 1973, 1974; Kacser & Burns 1973) as a means of understanding the contribution of the individual steps of a biochemical pathway to the values of flux and metabolite concentrations observed, some 13 years were to pass before we first surveyed (Kell & Westerhoff, 1986a b) how the formalism, tools and terms of metabolic control analysis might usefully be applied to such systems in a biotechnological context. Since another such period has now elapsed, it is timely to take stock of progress, to recognize that the take-up of these methods among biotechnologists has been less than widespread, and (as requested by the Editors) to give a personal and critical review of successes, failures, problems and prospects for the use of metabolic control analysis in biotechnology. In what follows, it is taken that the reader has a good working knowledge of the essential principles of metabolic control analysis, as summarized for instance in Kell & Westerhoff (1986a), Kell et al. (1989), Cornish-Bowden & Cárdenas (1990), Fell (1992, 1997), and Heinrich & Schuster (1996.); similar information is available on the Internet at http://gepasi.dbs.aber.ac.uk/metab/mca_home.htm and in links therefrom. In addition, we shall concentrate on unicellular systems, implicitly those most commonly exploited to make products of biotechnological interest.
Article FootNote
So the first requirement will be for a theoretical framework in which to embed all the detailed knowledge we have accumulated, to allow us to compute outcomes of the complex interactions and to start to understand the dynamics of the system. The second will be to make parallel measurements of the behaviour of many components during the execution by the cell of an integrated action in order to test whether the theory is right. Is there some other approach? If I knew it I would be doing it, and not writing about the problem.
Sydney Brenner (1997)
But one thing is certain: to understand the whole you must look at the whole.
Henrik Kacser (1986)
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Kell, D.B., Mendes, P. (2000). Snapshots of Systems. In: Cornish-Bowden, A., Cárdenas, M.L. (eds) Technological and Medical Implications of Metabolic Control Analysis. NATO Science Series, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4072-0_1
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