麦角酰胺产生菌Claviceps paspali的复合诱变及理性筛选

麦角酰胺是由麦角菌(Claviceps paspali)所产生的次级代谢产物,具有多种药理活性,目前已广泛用于治疗神经内分泌、脑血管系统的疾病以及产后止血,同时还作为原料用于合成其他重要药物。根据麦角酰胺的生物合成途径,以麦角酰胺产生菌HY17-3为初始菌株,经紫外诱变(UV)与甲基磺酸乙酯(EMS)复合诱变后,逐步筛选出乙酸钠、5-甲基色氨酸、丁二酸、山梨醇以及麦角酸的耐受株,最终得到高产菌株HY73-9,其摇瓶发酵效价达到590μg·mL-1,与初始菌株HY17-3(300μg·mL-1)相比,麦角酰胺的产量提高了97%。通过传代实验表明该菌株的高产遗传特性稳定。发酵罐发酵(30 L)实验显示麦角酰胺的产量可达815μg·mL-1,与初始菌株HY17-3相比,产量提高了172%。研究对于利用Claviceps paspali进行麦角酰胺的工业化生产具有重要意义。

Improvement of lysergic amide-producing Claviceps paspali by rational screening of ultraviolet and chemically induced mutants

Ergot alkaloids,which are produced by a wide range of fungi Clavicipitaceae and possess a variety of pharmacological activities,has been widely used to treat neuroendocrine,cerebrovascular diseases(such as Alzheimer's disease) and postpartum bleeding.Meanwhile,they are also used as the raw material for the synthesis of other important drugs.According to the biosynthetic pathway of lysergic amide,a rational screening procedure with UV irradiation and ethyl methane sulphonate(EMS) mutation was performed to obtain high lysergic amide producing starains.Sodium acetate mutants,5-methyl-tryptophan mutants,succinic acid mutants,sorbitol mutants and lysergic acid mutants were selected successively.A strain HY73-9 was obtained and its production of lysergic amide reached 584 μg·mL-1,which was 97% higher than that of the ancestral strain HY17-3.The subculture experiments indicated that the hereditary characteristic of high productivity of HY73-9 was stable.The production of lysergic amide by HY73-9 in a 30 L fermentor could reach 815 μg·mL-1 after 360 h batch fermentation,which was 172% higher than that of ancestral strain HY17-3.