Experimental simulation of dissolved oxygen fluctuations in large fermentors: effect on Streptomyces clavuligerus

An experimental Monte Carlo method was used to study the effect of fluctuations in oxygen concentration on the synthesis of antibiotics by Streptomyces clavuligerus. Air was supplied to the culture in a 2-L fermentor in random cycles following the lognormal distribution in order to model the circulation within large production-scale vessels. Each cycle consisted of air supply for 5 s followed by no aeration for the balance of the cycle time which ranged from 8 to 44 s, with a mean time of 20 s. Comparable experiments were also conducted with constant period cycling of air and with continuous supply of air. The yields of cephamycin C and its precursor, penicillin N, were suppressed by the Monte Carlo simulation of circulation in a large tank, as compared to constant period cycling. The concentration of dissolved oxygen remained at a low, ca. 5% of saturation, for 5-10 h longer during the Monte Carlo experiment than during the periodic aeration experiment. The biosynthetic enzymes, which are sensitive to oxygen levels, were likely affected not only by the mean time of cycling but also by the distribution of the cycles.