New process control strategy used in a rapamycin fermentation

A high antibiotic expression level was obtained in a pilot-scale fermentati on process with Streptomyces. With a new supervisory computer control algor ithm, the agitation, aeration rate, vessel pressure, and culture temperatur e were automatically changed sequentially during the process, avoiding the dissolved oxygen (DO) limitation. A unique pH control strategy was also use d in the process, and cells grew and produced the secondary metabolite prod uct, rapamycin, over a wider pH range. The quantity of acid addition was ve ry small when the pH reached the higher limit, 6.8, and then the pH was dro pped and adjusted gradually by the culture itself towards the lower limit, 6.2. Due to the optimized culture environment the entire fermentation time was reduced, and the productivity was simultaneously increased. The harvest ed dry cell weight was over 25 g/l and intracellular rapamycin was over 110 mg/l. (C) 1999 Elsevier Science Ltd. All rights reserved.