亚精胺,一种聚阳离子和多胺家族的重要成员,在多种生物中生存必不可少,并参与细胞生长和代谢的调节。探讨亚精胺对灵芝灵芝酸(GA)生物合成的调控机制,研究了亚精胺对GA和活性氧(ROS)含量的影响。我们的数据表明亚精胺促进线粒体ROS的产生并正调节GA的生物合成。进一步的研究表明,亚精胺促进线粒体复合物I和II的翻译,并随后影响其活性。在亚精胺合酶基因(spds)敲除菌株中,真核翻译起始因子5A(eIF5A)的过度抑制减少了50%以上,线粒体复合物I和II的活性降低了近60%和80%,分别,蛋白质含量减少了50%以上,这表明亚精胺对线粒体复合物I和II的影响是通过其对eIF5A催眠的影响而介导的。此外,击倒eIF5A后,脱氧盐酸合酶基因(dhs),和脱氧羟尿嘧啶羟化酶基因(dohh),线粒体ROS水平降低了近50%,GA含量减少了40%以上,这表明eIF5A催眠有助于线粒体ROS的产生和GA的生物合成。总之,亚精胺通过eIF5A催眠调节复合物I和II的翻译和随后的活性来维持线粒体ROS稳态,并通过线粒体ROS信号促进GA生物合成。本发现为亚精胺介导的次生代谢产物的生物合成提供了新的见解。重要性亚精胺是生物体生存所必需的,并参与各种生物过程的调节。然而,亚精胺各种生理功能的具体机制知之甚少,尤其是微生物。在这项研究中,我们发现亚精胺可抑制eIF5A促进线粒体ROS的产生,并随后调节微生物的次生代谢。我们的研究对亚精胺调节线粒体功能的机制提供了更好的理解,并为亚精胺介导的次生代谢产物的生物合成提供了新的见解。
Spermidine, a kind of polycation and one important member of the polyamine family, is essential for survival in many kinds of organisms and participates in the regulation of cell growth and metabolism. To explore the mechanism by which spermidine regulates ganoderic acid (GA) biosynthesis in Ganoderma lucidum, the effects of spermidine on GA and reactive oxygen species (ROS) contents were examined. Our data suggested that spermidine promoted the production of mitochondrial ROS and positively regulated GA biosynthesis. Further research revealed that spermidine promoted the translation of mitochondrial complexes I and II and subsequently influenced their activity. With a reduction in eukaryotic translation initiation factor 5A (eIF5A) hypusination by over 50% in spermidine synthase gene (spds) knockdown strains, the activities of mitochondrial complexes I and II were reduced by nearly 60% and 80%, respectively, and the protein contents were reduced by over 50%, suggesting that the effect of spermidine on mitochondrial complexes I and II was mediated through its influence on eIF5A hypusination. Furthermore, after knocking down eIF5A, the deoxyhypusine synthase gene (dhs), and the deoxyhypusine hydroxylase gene (dohh), the mitochondrial ROS level was reduced by nearly 50%, and the GA content was reduced by over 40%, suggesting that eIF5A hypusination contributed to mitochondrial ROS production and GA biosynthesis. In summary, spermidine maintains mitochondrial ROS homeostasis by regulating the translation and subsequent activity of complexes I and II via eIF5A hypusination and promotes GA biosynthesis via mitochondrial ROS signaling. The present findings provide new insight into the spermidine-mediated biosynthesis of secondary metabolites. IMPORTANCE Spermidine is necessary for organism survival and is involved in the regulation of various biological processes. However, the specific mechanisms underlying the various physiological functions of spermidine are poorly understood, especially in microorganisms. In this study, we found that spermidine hypusinates eIF5A to promote the production of mitochondrial ROS and subsequently regulate secondary metabolism in microorganisms. Our study provides a better understanding of the mechanism by which spermidine regulates mitochondrial function and provides new insight into the spermidine-mediated biosynthesis of secondary metabolites.