Department of Microbiology, The University of Georgia, Athens, Georgia, USA.
Department of Microbiology, The University of Georgia, Athens, Georgia, USA
J Bacteriol. 2020 Oct 22;202(22). doi: 10.1128/JB.00383-20.
YggS (COG0325) is a pyridoxal 5'-phosphate (PLP)-binding protein proposed to be involved in homeostasis of B vitamers. In , lack of resulted in phenotypes that were distinct and others that were similar to those of a mutant of Like other organisms, mutants of accumulate endogenous pyridoxine 5'-phosphate (PNP). Data herein show that strains lacking YggS accumulated ∼10-fold more PLP in growth medium than a parental strain. The deoxyxylulose 5-phosphate-dependent biosynthetic pathway for PLP and the PNP/pyridoxamine 5'-phosphate (PMP) oxidase credited with interconverting B vitamers were replaced with a single PLP synthase from The impact of a deletion on the intracellular and extracellular levels of B vitamers in this restructured strain supported a role for PdxH in PLP homeostasis and led to a general model for YggS function in PLP-PMP cycling. Our findings uncovered broader consequences of a mutation than previously reported and suggest that the accumulation of PNP is not a direct effect of lacking YggS but rather a downstream consequence. Pyridoxal 5'-phosphate (PLP) is an essential cofactor for enzymes in all domains of life. Perturbations in PLP or B vitamer content can be detrimental, notably causing B-dependent epilepsy in humans. YggS homologs are broadly conserved and have been implicated in altered levels of B vitamers in multiple organisms. The biochemical activity of YggS, expected to be conserved across domains, is not yet known. Herein, a simplified heterologous pathway minimized metabolic variables and allowed the dissection of this system to generate new metabolic knowledge that will be relevant to understanding YggS.
YggS（COG0325）是一种吡哆醛 5'-磷酸（PLP）结合蛋白，据推测它参与 B 族维生素的体内平衡。在[生物名称]中，缺乏[基因名称]导致的表型既独特又与[生物名称]的[基因突变名称]突变体的表型相似。与其他生物体一样，[生物名称]的突变体积累内源性吡哆醇 5'-磷酸（PNP）。本文数据显示，缺乏 YggS 的菌株在生长培养基中积累的 PLP 比亲本菌株多约 10 倍。PLP 和 PNP/吡哆醛 5'-磷酸（PMP）氧化酶的依赖于脱氧木酮糖 5-磷酸的生物合成途径被来自[生物名称]的单一 PLP 合酶取代。在这种重构的菌株中，缺失对细胞内和细胞外 B 族维生素水平的影响支持了 PdxH 在 PLP 体内平衡中的作用，并导致了 YggS 在 PLP-PMP 循环中的功能的一般模型。我们的发现揭示了[基因突变]比以前报道的更广泛的后果，并表明 PNP 的积累不是缺乏 YggS 的直接影响，而是下游的结果。吡哆醛 5'-磷酸（PLP）是所有生命领域中酶的必需辅因子。PLP 或 B 族维生素含量的波动可能是有害的，特别是在人类中会导致 B 依赖性癫痫。YggS 同源物广泛保守，并与多种生物体中 B 族维生素水平的改变有关。YggS 的生化活性，预计在各个领域都是保守的，但仍不清楚。在此，简化的异源途径最大限度地减少了代谢变量，并允许对该系统进行剖析，以产生新的代谢知识，这将有助于理解 YggS。
