Abstract The sequential simplex method is a useful tool for rapidly optimizing a process by moving through factor space via a relatively simple geometric algorithm. This method was employed to optimize growth and survivin-BCCP production in Escherichia coli Origami B using zinc sulphate supplemented culture medium. Five experimental parameters were investigated: concentration of zinc sulphate and IPTG, pH, temperature, and agitation rate. Optimized conditions were as follows: 190 μM zinc sulphate with 246 μM IPTG, pH 7, at a temperature of 23.5 °C and agitation rate of 345 rpm. The results for cell density and survivin-BCCP production were, 17% and 140% higher than in non-zinc supplemented medium and 12.6% and 25.5% higher than could be obtained by varying one-factor-at-a-time. The present work demonstrates the effectiveness of zinc sulphate supplementation and the efficiency of the sequential simplex optimization method in obtaining high yields.