Snapshots of Systems

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 & Cardenas (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.