Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, 113-8657, Japan.
Sci Rep. 2022 Oct 27;12(1):17411. doi: 10.1038/s41598-022-22108-0.
Microorganisms and plants produce siderophores, which function to transport environmental iron into cells as well as participate in cellular iron use and deposition. Their biological functions are diverse although their role in primary metabolism is poorly understood. Ferrichrome is a fungal-type siderophore synthesized by nonribosomal peptide synthetase (NRPS). Herein we show that ferrichrome induces adaptive growth of fission yeast on high ammonium media. Ammonium is a preferred nitrogen source as it suppresses uptake and catabolism of less preferred nitrogen sources such as leucine through a mechanism called nitrogen catabolite repression (NCR). Therefore, the growth of fission yeast mutant cells with leucine auxotrophy is suppressed in the presence of high concentrations of ammonium. This growth suppression was canceled by ferrichrome in a manner dependent on the amino acid transporter Cat1. Additionally, growth retardation of wild-type cells by excess ammonium was exacerbated by deleting the NRPS gene sib1, which is responsible for the biosynthesis of ferrichrome, suggesting that intrinsically produced ferrichrome functions in suppressing the metabolic action of ammonium. Furthermore, ferrichrome facilitated the growth of both wild-type and sib1-deficient cells under low glucose conditions. These results suggest that intracellular iron regulates primary metabolism, including NCR, which is mediated by siderophores.
微生物和植物产生铁载体，其功能是将环境中的铁运输到细胞内，并参与细胞内铁的利用和沉积。尽管它们在初级代谢中的作用尚未得到充分理解，但它们的生物学功能是多种多样的。 三羟甲基氨基甲烷是一种由非核糖体肽合成酶（NRPS）合成的真菌型铁载体。本文中我们表明，三羟甲基氨基甲烷诱导裂殖酵母在高铵培养基上适应性生长。铵是一种首选的氮源，因为它通过一种称为氮分解代谢阻遏（NCR）的机制抑制对较不优选的氮源（如亮氨酸）的摄取和分解代谢。因此，具有亮氨酸营养缺陷的裂殖酵母突变细胞在高浓度铵存在下的生长受到抑制。这种生长抑制可以通过氨基酸转运蛋白 Cat1 依赖的方式被三羟甲基氨基甲烷取消。此外，负责合成三羟甲基氨基甲烷的 NRPS 基因 sib1 的缺失加剧了野生型细胞因过量铵引起的生长迟缓，表明内源性产生的三羟甲基氨基甲烷在抑制铵的代谢作用中起作用。此外，三羟甲基氨基甲烷促进了野生型和 sib1 缺陷细胞在低糖条件下的生长。这些结果表明，细胞内铁调节包括 NCR 在内的初级代谢，这是由铁载体介导的。
