DESIGNING METABOLISM - ALTERNATIVE CONNECTIVITIES FOR THE PENTOSE-PHOSPHATE PATHWAY

We present a method for generating alternative biochemical pathways be tween specified compounds. We systematically generated diverse alterna tives to the nonoxidative stage of the pentose phosphate pathway, by f irst finding pathways between 5-carbon and 6-carbon skeletons. Each so lution of the equations for the stoichiometric coefficients of skeleto n-changing reactions defines a set of networks. Within each set we sel ected networks with modules, a module is a coupled set of reactions th at occurs more than one in a network. The networks can be classified i nto at least 53 families in at least seven superfamilies, according to the number, the input-output relations, and the internal structure of their modules. We then assigned classes of enzymes to mediate transfo rmations of carbon skeletons and modifications of functional groups. T he ensemble of candidate networks was too large to allow complete dete rmination of the optimal network. However, among the networks we studi ed the real pathway is especially favorable in several respects. It ha s few steps, uses no reducing or oxidizing compounds, requires only on e ATP in one direction of flux, and does not depend on recurrent input s. (C) 1998 Society for Mathematical Biology.