DYNAMIC REACTION DESIGN OF ENZYMATIC BIOTRANSFORMATIONS IN ORGANIC MEDIA - EQUILIBRIUM-CONTROLLED SYNTHESIS OF ANTIBIOTICS BY PENICILLIN-G ACYLASE

Parameters relevant to the thermodynamically controled synthesis of ce phalothin utilizing highly active stabilized penicillin G acylase deri vatives were studied. These included solubility/stability of substrate s, enzyme derivative activity/stability, reaction course and synthetic yields. These parameters were altered by varying the pH, dimethylform amide concentration and temperature. Simultaneous optimization of the selected parameters could not be achieved with a single set of conditi ons. However, continuous adjustment of conditions throughout the react ion course allowed each parameter to be optimized (dynamic reaction de sign). This strategy works by optimizing those parameters that are cri tical to the overall reaction at a given point, whilst leaving others sub-optimal when their contribution to the total is minimal. This stra tegy has achieved a 90% transformation of antibiotic nucleus to cephal othin at a final concentration of 20 g/l, high enzyme and reactant sta bility, with a reaction period of 3 h (using 1 ml of derivative/40 ml of reaction solution).