关键词: 西索米星, 生物合成, 分批发酵, 流加发酵

Abstract: 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.

Key words: sisomicin, biosynthesis, batch fermentation, fed-batch fermentation