一株高产洛伐他汀红曲霉的筛选与液态发酵条件优化  

Screening and liquid fermentation condition optimization of a high lovastatin producing Monascus

作　　者：毛继龙 张建辉 王璨 赵芃 陈文静 邱忠平[1] MAO Jilong;ZHANG Jianhui;WANG Can;ZHAO Peng;CHEN Wenjing;QIU Zhongping(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,Sichuan,China;Chengdu Third People’s Hospital,Chengdu 610081,Sichuan,China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031 [2]成都市第三人民医院,四川成都610081

出　　处：《微生物学通报》2022年第6期2221-2232,共12页Microbiology China

基　　金：国家自然科学基金面上项目(51978576);四川省重点研发计划(2019YFN0027)。

摘　　要：【背景】洛伐他汀(lovastatin)是红曲霉的次生代谢产物,是重要的临床用降血脂药物。在液态发酵条件下,红曲霉的洛伐他汀产量较低,难以满足工业化生产的要求。【目的】筛选获得一株高产洛伐他汀的红曲霉株,并通过优化液态发酵条件提高洛伐他汀的产量。【方法】从红曲米中筛选获得一株高产洛伐他汀的红曲霉株,依据形态学特征、生理生化特性及18S rRNA基因序列分析对分离菌株进行鉴定;通过响应面法对其产洛伐他汀的液态发酵条件进行优化。【结果】获得一株产洛伐他汀的紫红曲霉(Monascus purpureus M4),该菌在甘油57.80g/L、酵母浸粉5.52 g/L、接种量为6.90%条件下,洛伐他汀产量(173.60 mg/L)较优化前提高了4.8倍。【结论】菌株M4产洛伐他汀最优液态发酵条件的建立,为洛伐他汀的大规模生产及该菌株的工业化应用提供了技术支撑。[Background] Lovastatin is a secondary metabolite of Monascus and an important clinically used lipid-lowering drug. Under liquid fermentation conditions, the production of lovastatin from Monascus is low, which is difficult to meet the requirements of industrial production. [Objective] In this study, a Monascus strain with high lovastatin yield was screened, and the production of lovastatin was improved by optimizing liquid fermentation conditions. [Methods] A high lovastatin yielding Monascus strain was selected from red yeast rice, which was identified based on morphological characteristics,physiological and biochemical characteristics, and 18S rRNA gene sequence analysis, response surface methodology(RSM) was applied for the optimization of the liquid fermentation conditions for lovastatin production. [Results] A lovastatin-producing fungus(Monascus purpureus M4) was obtained. With glycerol at 57.80 g/L, yeast extract powder at 5.52 g/L, and inoculation size at 6.90%, the lovastatin output(173.60 mg/L) was 4.8 times higher than that before optimization. [Conclusion] The establishment of the optimal liquid fermentation conditions for lovastatin production by strain M4 provided technical support for the large-scale production of lovastatin and the industrial application of the strain.

关 键 词：红曲霉 洛伐他汀 液态发酵 响应面法 

分 类 号：TQ460.1[化学工程—制药化工] TQ920.1[轻工技术与工程—发酵工程]