抗生素AGPM生物合成的代谢调控研究

Studies on Regulation of Antibiotic AGPM Biosynthesis

探讨了葡萄糖、铵离子及磷酸盐对抗生素AGPM生物合成的调控作用和机理。结果表明当葡萄糖、铵离子和磷酸盐浓度分别大于20 gL-1、20mmolL-1和25mmolL-1时,对抗生素AGPM合成均产生抑制作用。加入葡萄糖衍生物进一步证明葡萄糖的调控作用主要是通过其磷酸化过程来实现的;而对比分析不同铵离子浓度下细胞内酶活力则发现铵离子抑制糖代谢中的EMP途径和HMP途径有关酶,却刺激TCA循环关键酶;若培养基存在高浓度的磷酸盐时,胞内的6-磷酸葡萄糖会大量积累,说明糖进一步代谢受阻从而抑制抗生素合成。上述结果表明抗生素AGPM形成与营养组分浓度密切相关,而葡萄糖、铵离子和磷酸盐对其合成的调控主要是通过调节初级代谢控制抗生素合成前体浓度来达到调控目的的。

To improve antibiotic AGPM production, the regulation of glucose, ammonium, and phosphate was studied. The results show that AGPM biosynthesis is inhibited by high concentration of glucose (>20gL-1), ammonium(>20mmolL-1)or phosphate (>25mmolL-1). By analysis of the activities of key enzymes and changes of metabolite concentration, the regulation mechanisms of them were testified as follows: the regulation of glucose is in effect through its phosphorylation; and ammonium inhibites some key enzymes in EMP and HMP pathways while activates enzymes of TCA pathways; high concentration of phosphate in medium causes accumulation of 6-phosphoglucose in vivo, finally inhibites glycolysis. All these courses led to absence of the precursors for AGPM biosynthesis, then affect antibiotic synthesis. Thus, to increase precursors accumulation and AGPM production, it is need to control medium components and screening strains which have the behaviors of deleting feedback of 6-phosphoglucose, high activities of EMP and HMP pathways, but low activity of TCA.