Zou Xiang, Hang Hai-feng, Chu Ju, Zhuang Ying-ping, Zhang Si-liang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China.
Bioresour Technol. 2009 Feb;100(3):1406-12. doi: 10.1016/j.biortech.2008.09.017. Epub 2008 Oct 16.
Effects of different nitrogen sources on the erythromycin production were investigated in 50 l fermenter with multi-parameter monitoring system firstly. With the increase of soybean flour concentration from 27 g/l to 37 g/l to the culture medium, the erythromycin production had no obvious increase. Whereas adding corn steep liquor 15 g/l in the medium was beneficial for the production of erythromycin, the maximum erythromycin production was 22.2% higher than that of the control. It was found that corn steep liquor can regulate and enhance the oxygen uptake rate (OUR) which characterizes the activity of the microbial metabolism by inter-scale observation and data association. Both Intracellular and extracellular organic acids of central metabolism were analyzed, and it was found that the whole levels of lactic acid, pyruvic acid, citric acid, and propionic acid were higher than those of control before 64th h. The consumption amount of amino acids, which could be transformed into the precursors for erythromycin synthesis (i.e. threonine, serine, alanine, glycine and phenylalanine), were elevated compared with the control in erythromycin biosynthesis phase. The results indicated that corn steep liquor can regulate OUR to certain level in the early phase of fermentation, and enhance the metabolic flux of erythromycin biosynthesis. Erythromycin production was successfully scaled up from a laboratory scale (50 l fermenter) to an industrial scale (132 m(3) and 372 m(3)) using OUR as the scale-up parameter. Erythromycin production on industrial scale was similar to that at laboratory scale.
首先在配备多参数监测系统的50升发酵罐中研究了不同氮源对红霉素生产的影响。随着培养基中大豆粉浓度从27克/升增加到37克/升，红霉素产量没有明显增加。然而，在培养基中添加15克/升玉米浆有利于红霉素的生产，最大红霉素产量比对照高22.2%。通过跨尺度观察和数据关联发现，玉米浆可以调节并提高表征微生物代谢活性的氧摄取率（OUR）。分析了中心代谢的细胞内和细胞外有机酸，发现在第64小时之前，乳酸、丙酮酸、柠檬酸和丙酸的整体水平均高于对照。在红霉素生物合成阶段，与对照相比，可转化为红霉素合成前体（即苏氨酸、丝氨酸、丙氨酸、甘氨酸和苯丙氨酸）的氨基酸消耗量有所增加。结果表明，玉米浆可以在发酵早期将OUR调节到一定水平，并增强红霉素生物合成的代谢通量。以OUR作为放大参数，红霉素生产成功地从实验室规模（50升发酵罐）扩大到工业规模（132立方米和372立方米）。工业规模的红霉素产量与实验室规模相似。
