氨基酸添加对吸水链霉菌5008发酵过程中有效霉素A合成的影响

氨基糖苷类抗生素的生物合成与氨基酸代谢密切相关,通过在吸水链霉菌5008发酵过程中分别添加9种不同种类氨基酸,研究了氨基酸对有效霉素A生物合成的影响。结果表明,在这9种氨基酸中,有7种氨基酸对有效霉素A产量有提升作用。其中异亮氨酸对产量提升幅度最大,与对照组相比,可以将产量提高约49%(16.76 g/L);同时发现甲硫氨酸对有效霉素A产量有着明显的抑制作用,与对照相比,将产量降低约25%(8.47 g/L);随后对添加氨基酸发酵过程中蛋白积累量,糖利用量以及有效霉素A前体合成相关碳代谢途径的酶活力情况进行检测,结果显示氨基酸能够影响碳代谢途径上关键酶的活性,导致碳代谢流向改变,从而促进有效霉素A前体的积累与有效霉素A的生物合成。

Effects of amino acids on the biosynthesis of validamycin A in the fermentation of Streptomyces hygroscopicus 5008

There is a close relationship between amino acid metabolism and aminoglycoside antibiotic biosynthesis.Nine kinds of amino acids were added during the fermentation of Streptomyces hygroscopicus 5008 to investigate effects of amino acids on biosynthesis of validamycin A(Val-A).Among these nine kinds of amino acids,seven kinds of them could promote Val-A production.The addition of isoleucine was found to promote Val-A production most to 16.76 g/L which increased by 49% compared to the control.Besides,the addition of methionine showed inhibition on Val-A biosynthesis.Compared to the control,Val-A productivity in methionine addition fermentation decreased by 25% to 8.47 g/L.To further understand the impact of amino acids on Val-A biosynthesis,a series of analysis on protein accumulation,sugar utilization and activities of key enzymes in carbon metabolism which are related to Val-A precursor synthesis,were done.The results revealed addition of amino acids could affect activities of key enzymes in carbon metabolism and redirect their flux which benefits to accumulation of Val-A precursor and stimulates biosynthesis of Val-A.