Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan
Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan.
Appl Environ Microbiol. 2019 May 16;85(11). doi: 10.1128/AEM.00430-19. Print 2019 Jun 1.
YggS (COG0325) is a member of the highly conserved pyridoxal 5'-phosphate (PLP)-binding protein (PLPBP) family. Recent studies suggested a role for this protein family in the homeostasis of vitamin B and amino acids. The deletion or mutation of a member of this protein family causes pleiotropic effects in many organisms and is causative of vitamin B-dependent epilepsy in humans. To date, little has been known about the mechanism by which lack of YggS results in these diverse phenotypes. In this study, we determined that the pyridoxine (PN) sensitivity observed in -deficient was caused by the pyridoxine 5'-phosphate (PNP)-dependent overproduction of Val, which is toxic to The data suggest that the mutation impacts Val accumulation by perturbing the biosynthetic of Thr from homoserine (Hse). Exogenous Hse inhibited the growth of the mutant, caused further accumulation of PNP, and increased the levels of some intermediates in the Thr-Ile-Val metabolic pathways. Blocking the Thr biosynthetic pathway or decreasing the intracellular PNP levels abolished the perturbations of amino acid metabolism caused by the exogenous PN and Hse. Our data showed that a high concentration of intracellular PNP is the root cause of at least some of the pleiotropic phenotypes described for a mutant of Recent studies showed that deletion or mutation of members of the YggS protein family causes pleiotropic effects in many organisms. Little is known about the causes, mechanisms, and consequences of these diverse phenotypes. It was previously shown that mutations in result in the accumulation of PNP and some metabolites in the Ile/Val biosynthetic pathway. This work revealed that some exogenous stresses increase the aberrant accumulation of PNP in the mutant. In addition, the current report provides evidence indicating that some, but not all, of the phenotypes of the mutant in are due to the elevated PNP level. These results will contribute to continuing efforts to determine the molecular functions of the members of the YggS protein family.
YggS（COG0325）是高度保守的吡哆醛 5'-磷酸（PLP）结合蛋白（PLPBP）家族的成员。最近的研究表明，该蛋白家族在维生素 B 和氨基酸的动态平衡中起作用。该蛋白家族成员的缺失或突变会导致许多生物体的多效性效应，并导致人类维生素 B 依赖性癫痫。迄今为止，对于缺乏 YggS 如何导致这些不同表型的机制知之甚少。在这项研究中，我们确定在ΔyggS 中观察到的吡哆醇（PN）敏感性是由 PN 依赖性的 Val 过度产生引起的，这对ΔyggS 是有毒的。数据表明，突变通过干扰从高丝氨酸（Hse）到苏氨酸（Thr）的生物合成来影响 Val 积累。外源性 Hse 抑制ΔyggS 突变体的生长，导致 PNP 进一步积累，并增加 Thr-Ile-Val 代谢途径中的一些中间产物的水平。阻断 Thr 生物合成途径或降低细胞内 PNP 水平消除了外源性 PN 和 Hse 引起的氨基酸代谢扰动。我们的数据表明，细胞内 PNP 的高浓度是至少一些描述的ΔyggS 突变体的多效性表型的根本原因。最近的研究表明，YggS 蛋白家族成员的缺失或突变会导致许多生物体的多效性效应。对于这些不同表型的原因、机制和后果知之甚少。以前的研究表明，ΔyggS 中的突变导致 PNP 和 Ile/Val 生物合成途径中的一些代谢物积累。这项工作表明，一些外源性应激会增加ΔyggS 突变体中异常的 PNP 积累。此外，本报告提供的证据表明，ΔyggS 突变体的一些但不是所有表型是由于 PNP 水平升高引起的。这些结果将有助于继续努力确定 YggS 蛋白家族成员的分子功能。
