西索米星发酵工艺条件的优化

考察了氯化钴、蛋氨酸、磷酸盐和可发酵糖对西索米星分批发酵的影响，优化了西索米星分批发酵工艺条件. 研究表明，初始发酵培养基中添加6~10 mg/L氯化钴或1.0~2.0 g/L蛋氨酸有助于西索米星的合成，蛋氨酸在产物合成前期添加的效果最佳. 高浓度磷酸盐会提高发酵液中淀粉水解酶活力和丙酮酸浓度、降低碱性磷酸酯酶活力和抑制西索米星的合成. 应分段控制发酵液中的磷酸盐浓度，在菌体生长期应控制在3.14 mmol/L以内，在产物合成期应控制在0.10 mmol/L以下. 与分批发酵过程相比，当以麦芽糖或淀粉水解液为补料液、将发酵液中可发酵糖浓度控制在8.5~11.5 g/L时，不论采用变流率还是恒流率的流加发酵方式均有助于大幅度提高西索米星发酵水平.

Optimization of Fermentation Conditions on Sisomicin Biosynthesis

The effects of cobaltous chloride, methionine, phosphate and fermentable sugar on sisomicin biosynthesis in a batch fermentation process were investigated. Fermentation conditions of sisomicin biosynthesis in a batch fermentation process were optimized. It was found that the supplementation with some components in medium was significant to sisomicin production. Methylation of precursor gentamicin A in sisomicin biosynthesis was stimulated by 6-10 mg/L cobaltous chloride or 1.0-2.0 g/L methionine. The best time of methionine supplementation was in the pre-middle stage of sisomicin biosynthesis. High phosphate concentration would result in high pyruvic acid concentration and amylase activity, and low alkaline phosphatase activity and sisomicin concentration. It is beneficial to sisomicin biosynthesis that the phosphate concentration is controlled under 3.14 mmol/L in cell growth phase and below 0.10 mmol/L in sisomicin biosynthesis phase. Compared with that in the batch fermentation, while fermentable sugar was controlled in 8.5-11.5 g/L, either at constant or varying maltose feeding rate or at constant starch hydrolysate feeding rate, the ferment level of sisomicin in the fed-batch fermentations was distinctly increased.