旁路代谢酶抑制剂对林可霉素发酵的影响

The effect of enzymatic inhibitors of metabolic side pathways on lincomycin production

目的研究林可链霉菌的发酵工艺,提高林可霉素的产量。方法在林可链霉菌发酵产林可霉素的过程中,在一定时间添加一定量的旁路代谢酶抑制剂丙氨酸和三甲胺,用生物效价法测定发酵液中林可霉素的产量。结果在发酵开始时添加0.01%的丙氨酸,同时在24h时添加0.02%的三甲胺,使林可霉素的产量提高26%。实验发现该种添加方法抑制了糖酵解途径中的丙酮酸激酶和莽草酸途径中的邻氨基苯甲酸合成酶的酶活,使菌体内积累高浓度的林可霉素的前体酪氨酸及L-多巴,进而提高了林可霉素的产量。结论该种发酵工艺使林可霉素产量得到显著提高。

Objective To study the fermentation process of Streptomyces lincolnensis and increase the production of lincomycin. Methods During the fermentation of Streptomyces lincolnensis, certain amount of enzymatic inhibitors of metabolic side pathways： alanine and trimethylamine were added at certain time, the production of lincomycin was determined by biological assays. Results Adding 0.01% alanine at the beginning of the fermentation, and then adding 0.02% trimethylamine at 24h of the fermentation, the production of lincomycin increased by 26%. The experiment showed that this adding method inhibited the activities of pyruvate kinase in glycolytic pathway and anthranilate synthase in shikimic acid pathway, and it resulted in high concentrations of lincomycin precursors： tyrosine and L-dopa accumulated in mycelia, which led to the increase in the production of lincomycin. Conclusion This fermentation process can dramatically increase the production of lincomycin.