酿酒酵母工程菌产青蒿酸的发酵动力学研究

Fermentation kinetics for artemisinic acid production by engineered Saccharomyces cerevisiae

以青蒿酸产量为考察指标,在50 L发酵罐中对酿酒酵母(Saccharomyces cerevisiae)工程菌1211发酵产青蒿酸的溶氧参数进行优化。在此基础上,根据Logistic方程及Luedeking-Piret方程构建酿酒酵母工程菌1211分批发酵产青蒿酸的动力学模型。结果表明,当溶氧参数为25%~30%时,青蒿酸产量最高,为(6 269.6±100.3)mg/L。青蒿酸合成与菌体生长呈现部分生长偶联型。通过Origin 9.0软件对动力学模型进行非线性拟合,发现S. cerevisiae工程菌1211的菌体繁殖生长、青蒿酸合成以及基质消耗动力学模型的拟合度R2分别达到了0.995 85、0.979 04和0.995 48,该动力学模型能够很好的描述S. cerevisiae工程菌1211分批发酵过程。该研究为青蒿酸的低成本发酵及工业化大规模发酵生产提供了理论基础。

With the yield of artemisinic acid as the evaluation index, the dissolved oxygen parameters for artemisinic acid production by fermentation of engineered Saccharomyces cerevisiae in 50 L fermenter was optimized. On this basis, according to Logistic equation and Luedeking-Piret equation, the kinetic model of artemisinic acid production by batch fermentation of engineered S. cerevisiae 1211 was established. Results showed that the yield of artemisinic acid was the highest of(6 269.6±100.3) mg/L when the dissolved oxygen levels were maintained at 25%-30%. The synthesis of artemisinic acid and the cell growth showed partial growth coupling. The kinetic model was nonlinearly fitted by the Origin 9.0 software, and the results showed that the goodness-of-fit scores R2 of the growth of engineered S. cerevisiae 1211, artemisinic acid synthesis and matrix consumption models were 0.995 85,0.979 04 and 0.995 48, respectively, indicating that the models could provide a reasonable description for the batch fermentation of engineered S. cerevisiae1211. The study provided a theoretical basis for the low-cost fermentation and large-scale industrial production of artemisinic acid.