响应面法优化海洋镰刀腐皮菌产出HMG-CoA还原酶抑制剂的培养条件

Use of response surface methodology on the production of active compound MFS from Fusarium solani and its activity on HMG-CoA reductase

摘要:

【目的】采用响应面法对海洋微生物镰刀腐皮菌FG319发酵产生MFS (Metabolite of Fusarium solani FG319)培养条件进行优化。【方法】在单因素试验结果的基础上，依据Box-Behnken中心组合原则设计诱导物添加量、培养时间、培养温度的3因素3水平响应面实验，以MFS产出量为响应值优化镰刀腐皮菌FG319的培养条件。【结果】镰刀腐皮菌FG319最优培养条件为诱导物添加量0.6%、培养时间7 d、培养温度22 °C，在此培养条件下，MFS最高产量达到20.11 mg/L，是优化前的4倍，与理论预测的相对误差为0.64%，实测值与响应面预测值拟合良好。镰刀腐皮菌FG319代谢产物MFS在HMG-CoA还原酶和NADPH构筑的分子评价反应体系，当MFS添加到100 mg/L时，具有类似洛伐他汀抑制HMG-CoA还原酶的最大抑制率。【结论】响应面试验设计对镰刀腐皮菌FG319培养条件的优化是有效的，其次生代谢产物MFS体外抑制HMG-CoA还原酶的效果也是明显的。

Abstract:

[Objective] In the present study, response surface methodology (RSM) was used to optimize the fermentation conditions of MFS (metabolite of Fusarium solani FG319) extracted from marine microorganism, Fusarium solani. [Methods] On the basis of single factor tests, Box-Behnken RSM was employed with three factors such as addition of L-ornithine hydrochloride at different concentrations, culture time, and culture temperature on the yield of MFS. [Results] The optimum culture conditions were as follows: the L-ornithine hydrochloride addition was 0.6% (W/V), culture time was 7 d, culture temperature was 22 °C. Under these conditions the yield of MFS was 20.11 mg/L, which is 4 times increased than without any optimization and the relative error with the theoretical value was 0.64%. The inhibition rate of MFS on HMG-CoA reductase was achieved above 100 mg/L, and has a similar inhibition as Lovastatin. [Conclusion] The culture conditions obtained by response surface methodology were effective and reliable, and the effect of MFS on HMG-CoA reductase is obvious in vitro.