Yk. Yang et al., MAXIMUM VIRGINIAMYCIN PRODUCTION BY OPTIMIZATION OF CULTIVATION CONDITIONS IN BATCH CULTURE WITH AUTOREGULATOR ADDITION, Biotechnology and bioengineering, 49(4), 1996, pp. 437-444
A strategy for optimization of non-growth-associated production in bat
ch culture employing an empirical approach was developed through the s
tudy of virginiamycin production. The strategy is formulated with two
aims: attaining a high cell concentration at the beginning of the prod
uction phase without decrease in production activity; and enhancing th
e production activity during the production phase. As a practical exam
ple, the goal of a maximum virginiamycin (M and S) production in the b
atch culture of Streptomyces virginiae was set. To attain a high cell
concentration in the production phase of the batch culture, that is, t
o extend the growth phase for as long as possible, the optimum composi
tion and concentration of the complex medium, especially the yeast ext
ract (YE) concentration, were first investigated. Dissolved oxygen (DO
) concentration control was also a parameter considered in maintaining
the production activity during the production phase. In addition, to
enhance the production activity, an optimum addition strategy of an au
toregulator, virginiae butanolide-C (VB-C), was investigated. Combinin
g these measures, the optimum cultivation conditions were found to be
an initial YE concentration in the complex medium of 45 g/L, the shot
addition of 300 mu g/L of VB-C 11.5 h after the start of the batch cul
ture, and a DO concentration maintained above 2 mg/L. The maximum conc
entrations of virginiamycin M and S were about ninefold those obtained
under nonoptimum cultivation conditions. Nonoptimum cultivation condi
tions consisted of an initial YE concentration one sixth (7.5 g/L) tha
t of the optimum cultivation conditions, and no VB-C addition. These c
onditions were used as representative of the standard cultivation of v
irginiamycin in this study. The strategy developed here will be applic
able to the production of other antibiotics, especially to the cultiva
tion of Streptomyces species, in which a hormonelike signal material (
an autoregulator) plays an important role in antibiotic production. (C
) 1996 John Wiley & Sons, Inc.