A METABOLIC NETWORK STOICHIOMETRY ANALYSIS OF MICROBIAL-GROWTH AND PRODUCT FORMATION

Using available biochemical information, metabolic networks have been constructed to describe the biochemistry of growth of Saccharomyces cerevisiae and Candida utilis on a wide variety of carbon substrates. All networks contained only two fitted parameters, the P/O ratio and a maintenance coefficient. It is shown that with a growth-associated maintenance coefficient, K, of 1.37 mol ATP/C-mol protein for both yeasts and P/O ratios of 1.20 and 1.53 for S. cerevisiae and C. utilis, respectively, measured biomass yields could be described accurately. A metabolic flux analysis of aerobic growth of S. cerevisiae on glucose/ethanol mixtures predicted five different metabolic flux regimes upon transition from 100% glucose to 100% ethanol. The metabolic network constructed for growth of S. cerevisiae on glucose was applied to perform a theoretical exercise on the overproduction of amino acids. It is shown that theoretical operational product yield values can be substantially lower than calculated maximum product yields. A practical case of lysine production was analyzed with respect to theoretical bottlenecks limiting product formation. Predictions of network-derived irreversibility limits for Y-SP (mu) functions were compared with literature data. The comparisons show that in real systems such irreversibility constraints may be of relevance. It is concluded that analysis of metabolic network stoichiometry is a useful tool to detect metabolic limits and to guide process intensification studies. (C) 1995 John Wiley & Sons, Inc.