Optimization And Scale-up Of Bioprocess For Salinomycin Production By Streptomyces Albus

Salinomycin is a kind of polyether antibiotics which is popularly used as an agro-antibiotic because of its efficiency, broad spectrum against disease-causing bacteria and low residue in the soil. However, there are several bottleneck techniques encountered during the salinomycin production process nowadays, like high production cost and soybean oil as substrate. Therefore, the aim of this thesis is to enhance the productivity of salinomycin and to reduce the cost by medium optimization and culture conditions optimization for salinomycin fermentation on pilot scale plant and the production scale.First of all, a new recipe of culture medium was obtained through single factor experiment, orthogonal test, PB design and centeral composite design(CCD). The salinomycin titer was higher 20% using the new recipe than that with the old recipe and the amount of the oil used is 20g/L less than the original medium. The new medium and culture conditions are as follows: dextrin 45g/L, corn steep liquor 6g/L, soybean meal 3g/L, KCl 3g/L, NH4NO3 5g/L, KH2PO4 0 4g/L, soybean oil 100g/L, CaCO3 1g/L, inoculum 10%, pH controlled at 7.0, the shaking speed of 250 rpm and fermentation duration of 10d were determined.Two critical factors affecting the salinomycin biosynthesis were acquired in 50L fermentator. One is dissolved oxygen(DO) tension. Its optimum range is around 40%. The other is residual sugar concentration in the broth, which should be lower than 1%. Also, the feeding strategy was developed in 2m3 fermentor. The oil feed should start when the residual sugar was lower than 3%or CO2 evolution rate (CER) initially dropped with the feed rate of 8g/L/h in the early 100h of fermentation and the the feeding rate was shifted to 5g/L/h afterwards. Simultaneously, pH should be adjusted to 5.8 by ammonia feed and then 0.8% NaOH was used instead of ammonia when the biomass(PMV) reached 40%, which can lead to a low concentration of amino-N. There is a significant defference in salinomycin production and microbial physilogical characteristics between pilot scale fermentation and industrial production scale so that the new fermentation process established at pilot scale failed to be scaled-up in the 30m3 production fermentor. It was revealed by computational fluid dynamics (CFD) that the problems occurred in the 30m3 tank were poor mixing capability and oxygen transfer ability, which should be improved in our next work.