Optimization of industrial production of rifamycin B by Amycolatopsis mediterranei. IV. Production in the fermentor

Abstract

Optimization of the physical and physiological parameters of the fermentation process using the gene 
amplified variant of Amycolatopsis mediterranei (NCH) was carried out. Optimization of the physical 
parameters by controlling the pH at 6.5 for 3 days then at 7 thereafter and by adjustment of aeration at 1 
vvm for 3 days then controlling the dissolved oxygen (DO) at 30% saturation increased the yield from 
9.77 to 11.96 (22%) and 13.39 g/l (37%), respectively. Replacing 12% glucose in the fermentation 
medium (F2m1) with 5% glucose syrup (F2m3 medium) resulted in a drop of the yield from 9.77 to 7.5 
g/l, while further addition of another 5% glucose syrup at day 4 increased the yield from 7.5 to 13.81 g/l 
(84%); with a further increase in the yield to 14.25 g/l (90%) upon controlling DO. Whereas, the 
combined addition of 0.1% yeast extract at day 2 to F2m3 medium along with the addition 5% glucose 
syrup at day 4 increased the yield from 7.5 to 15.35 g/l (105%); with a further increase in the yield to 16.3 
g/l (117%) upon controlling DO. The fed-batch addition of both 3% soytone at day 3 and 5% of glucose 
syrup at day 4 to F2m3 medium increased the yield from 7.5 to 16.2 g/l (116%) and by extending the 
fermentation period to 10 days the yield reached 17.9 g/l (139%). Upon applying all optimum physical 
and physiological conditions in the fermentor the yield increased from 7.5 to 17.43 g/l in 8 days (132%) 
and by extending the fermentation period to 10 days the yield reached 19.4 g/l (159%). Further process 
optimization by examination and analysis of the kinetics of the process would most certainly further 
increase the yield and quantitatively define the process to a level that could be tested on a pilot scale.