他克莫司高产菌株的理性化选育

Rational screening for high production tacrolimus-producing strain

目的理性化选育他克莫司高产菌株。方法应用化学和物理诱变剂对他克莫司产生菌进行菌种诱变,并利用特定的选择剂即莽草酸和哌可酸及其相应的结构类似物作为选择压力筛选突变株。然后对特定的正突变株进行他克莫司生物合成的营养学研究。结果与结论获得一株高产突变株6H-23-7,它的他克莫司相对发酵效价比出发菌株弗氏链霉菌类群Streptomyces sp.FCZ0311提高了约2倍。

Objective To rational screen high production tacrolimus-producing strain. Methods It showed methods for screening for high production mutant of tacrolimus producer by chemical and physical mutagens, and by using specific selection agents including shikimic acid, pipecolic acid and their corresponding structural analogues as selection pressure, as well as by studying nutrition of tacrolimus biosynthesis on a definite positive mutant. Result and Conclusion A hi[gh production mutant, strain 6H-23-7 was obtained and the relative fermentation titer of tacrolimus was about 2 times higher than that of the starting, Streptomyces sp. FCZ0311.