常压室温等离子体诱变选育他克莫司高产菌株及发酵条件优化

目的 选育他克莫司高产菌株，提高发酵单位。方法 采用常压室温等离子体(ARTP)技术对一株他克莫司出发菌株FK13-2-14进行诱变，对高产菌株的种子瓶接种量、异亮氨酸的添加量及添加时间等发酵条件进行优化。结果 获得1株稳定的突变高产菌株FK18-1-56，摇瓶发酵单位提高了162%；优化后种子瓶接种量为1.5cm2/40mL，异亮氨酸添加时间为48h，添加量为3.0g/L。高产菌株在优化后的发酵条件下，100L罐发酵单位达到997μg/mL，比出发菌株提高了128%。结论 利用常压室温等离子体诱变技术得到他克莫司高产菌株，经发酵工艺优化后，大幅度提高了他克莫司的工业发酵水平。

Screening of a high-yielding tacrolimus producing strain using atmospheric room temperature plasma and optimization of fermentation conditions

Objective To obtain a high-yielding tacrolimus producing strain using mutation methods to improve the fermentation unit. Methods The primitive strain FK13-2-14 was treated using an atmospheric and room temperature plasmas (ARTP) technology. Fermentation conditions were optimized, such as the inoculation of seed bottles, the additive amount of isoleucine and the addition time. Results A high-yielding mutant, designated FK18-1-56, was successfully selected. Its fermentation production was 162% higher than that of the original strain in flask culture. The optimum fermentation conditions were determined as follows: the inoculation amount of seed bottles was 1.5cm2/40mL, the addition amount of isoleucine was 3.0g/L, and the addition time was 48h after fermentation. In a 100L fermenter, the production of tacrolimus reached 997μg/mL under the optimized conditions by the strain FK18-1-56. It was 128% higher than that of the original strain. Conclusion The high-yielding tacrolimus producing strain selected by ARTP will further substantially improve the industrial production of tacrolimus under the optimized