MODEL ANALYSIS CONCERNING THE EFFECTS OF GROWTH-RATE AND INTRACELLULAR TRYPTOPHAN LEVEL ON THE STABILITY AND DYNAMICS OF TRYPTOPHAN BIOSYNTHESIS IN BACTERIA

An extended mathematical model for the biosynthesis of tryptophan (trp ) in bacteria is proposed. The model considers both feedback inhibitio n of the biosynthetic enzymes and repression of the trp operon by tryp tophan and explicitly takes into account the growth rate and the deman d of tryptophan for protein synthesis. The intracellular concentration of tryptophan is found to drastically decline with the growth rate, p articularly at low values of growth rate. This also applies to genetic ally modified strains with reduced strain levels of the repressor and/ or alleviated feedback inhibition. At low growth rates the intracellul ar concentrations of tryptophan and the synthetic enzymes are also str ongly affected by the strain level of repressor, feedback inhibition a nd the consumption of tryptophan for protein synthesis. It can be conc luded that for an effective production of tryptophan the growth rate o f cells should be kept as low as possible. Another important factor fo r the production of tryptophan is the stability and dynamics of the tr p operon. Model analysis revealed that the intracellular concentration of tryptophan is determinant for the occurrence of oscillatory expres sion of the trp operon. Instability of tryptophan synthesis occurs at low intracellular tryptophan concentrations, irrespective of the growt h rate. A reduction of the repressor level can reduce the instability region so that a stable operation with improved production is possible . In addition, a high demand of tryptophan for protein synthesis shoul d be avoided which may lead to a periodic expression of the trp operon , even at low growth rate. (C) 1997 Elsevier Science B.V.