OPTIMUM AUTOREGULATOR ADDITION STRATEGY FOR MAXIMUM VIRGINIAMYCIN PRODUCTION IN BATCH CULTURE OF STREPTOMYCES-VIRGINIAE

Virginiae butanolides (VBs) are autoregulators of Streptomyces virgini ae, which induce virginiamycin biosynthesis. Generally, autoregulators are synthesized by the microorganism itself during culture. Addition of chemically synthesized virginiae butanolide-C (VB-C), which is one of the VBs, can also control the induction time and the amount of virg iniamycin production. The optimum concentration and shot-feeding time of VB-C for the maximum production of virginiamycins M and S were inve stigated in flasks and jar-fermenter batch cultures. VB-C addition lat er than 8 h from the start of culture induced not only virginiamycin M and S synthesis but also VB synthesis. Virginiamycin M and S producti on increased with the decrease of total VBs (produced VBs and added VB -C) concentration. That is, although VBs are needed to induce virginia mycin M and S synthesis, the amount of VB-C added should be such that as small an amount as possible of VBs is synthesized to achieve the ma ximum production of virginiamycins M and S. However, the VB-C addition earlier than 8 h from the start of culture showed no clear relationsh ip between the amounts of VBs and virginiamycins M and S produced. In conclusion, the maximum production of virginiamycins M and S was attai ned by the shot addition of 5 mu g/L VB-C at 8 h from the start of cul ture. The maximum value was about twofold that without VB-C addition. The optimum addition strategy of VB-C was confirmed by the jar-ferment er experiments. (C) 1995 John Wiley & Sons, Inc.