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机构地区:[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海201203 [2]中国药科大学,江苏南京211198
出 处:《中国医药工业杂志》2017年第12期1738-1743,共6页Chinese Journal of Pharmaceuticals
基 金:国家"重大新药创制"科技重大专项(2012ZX09201101-008);国家自然科学基金(81273413);上海市自然科学基金(14ZR1440200)
摘 要:本试验采用25 L自动发酵罐,在保持其他因素不变的前提下,通过调整发酵罐搅拌来控制发酵液的溶氧浓度。通过测定发酵过程中的溶氧浓度、菌体浓度、乙酸生成量、质粒稳定性及L-色氨酸(1)合成量等指标,确定了最适搅拌速度和搅拌桨大小。通过优化发酵搅拌条件,使得1的产量提高到了61.0 g/L。本研究为1的工业化生产优化提供了依据。Under the premise of keeping other factors unchanged, agitator blade and agitation were adjusted to control dissolved oxygen concentration in fermentation broth in the 25 L fermentation tank for the fermentation of L-tryptophan (1). The appropriate agitator blade size and stirring speed were confirmed with dissolved oxygen concentration, bacteria concentration, acetic acid concentration, stability of the plasmid and the yield of 1 during fermentation as the indicators. The optimized conditions provided appropriate dissolved oxygen concentration in the fermentation broth, and kept the producing strain a appropriate growth rate in the initial stage of fermentation. At the same time, the optimization measures kept the producing strain a higher growth rate and plasmid stability, with less acetic acid accumulation in the logarithmic growth phase. And the producing strain maintained a higher rate biosynthesis of 1 during the whole process of fermentation. Finally, the 1 production was increased to 61.0 g/L. Our work provides a basis for the industrial production of 1.
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