洛伐他汀高产菌株的选育

摘 要：为了提高红曲霉发酵生产洛伐他汀的能力，分别采用紫外线、亚硝酸、硫酸二乙酯对出发菌株（Monascus sp.）进行诱变处理。结果表明：3种诱变剂对Monascus sp.的诱变效果有较大差异，其中紫外线诱变效果最好，硫酸二乙酯次之，亚硝酸最差。通过筛选，得到2株高产突变株，分别命名为：Monascus sp.UV-5、Monascus sp.DE-8，其产量分别为 0.239 mg/mL、0.223 mg/mL，比原始菌株分别提高了42.3%、32.7 %。遗传稳定试验结果显示，Monascus sp.UV-5、Monascus sp.DE-8遗传性能较稳定，可应用于生产。

关键词：洛伐他汀；红曲霉；诱变；紫外线；硫酸二乙酯；亚硝酸

中图分类号 S511 文献标识码 A 文章编号 1007-7731（2017）12-0027-03

Abatract：In order to improve lovstatin yield of Monascus sp.，the starting strains were treated by treated by UV，HNO2 and DES respectively. The results showed that three kinds of Mutagens had different effects on Monascus sp.，UV had best mutagenesis effects，then was DES and HNO2 was the worst. Two high and stable yield mutants were obtained and named Monascus sp. UV-5 and Monascus sp.DE-8 respectively.The lovstatin yield of Monascus sp.UV-5，Monascus sp. DE-8 was 0.239mg/mL and 0.223 mg/mL，which increased 42.3% and 32.7% compared with the original strain.The consecutive culture of Monascus sp. UV-5，Monascus sp. DE-8 showed that genetic performance was stable and can be used in production.

Key words：Lovstatin；Monascus sp.；Mutagenesis；UV；DES；Nitrous acid

近年来，随着经济的高速发展，人民生活水平不断提高。我国民众的饮食结构发生了很大的改变，过多地摄入高热量、高脂质的食物，导致高血脂、高血压、冠心病等“富贵病”发病率显著增加。目前，临床上治疗该类疾病的主要是他汀类药物，最重要的是洛伐他汀。洛伐他汀（Lovastatin）是一类在临床上应用广泛的降血脂、降胆固醇药物，作为体内羟甲戊二酰辅酶A（HMG-CoA）的结构类似物，能竞争性抑制HMG-CoA的代谢，减少机体内胆固醇的生成，从而对高血压和冠心病等疾病起到积极的防治作用[1-4]。当前，洛伐他汀主要是通过微生物发酵生产，在微生物发酵中，优良的菌种是获得生产成功的关键[5]。诱变育种是获得高产菌株的简便有效的手段在微生物育种中被广泛应用。课题组采用多种诱变剂对洛伐他汀产生菌株红曲霉进行处理，以期获得稳定高产菌株，为进一步开发功能性红曲提供理论依据。

1 材料与方法

1.1 材料与仪器