The Role of YggS in Vitamin B

YggS (COG0325) is a pyridoxal 5′-phosphate (PLP)-binding protein proposed to be involved in homeostasis of B(6) vitamers. In Salmonella enterica, lack of yggS resulted in phenotypes that were distinct and others that were similar to those of a yggS mutant of Escherichia coli. Like other organisms, yggS mutants of S. enterica 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(6) vitamers were replaced with a single PLP synthase from Saccharomyces cerevisiae. The impact of a yggS deletion on the intracellular and extracellular levels of B(6) 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 yggS mutation than previously reported and suggest that the accumulation of PNP is not a direct effect of lacking YggS but rather a downstream consequence. IMPORTANCE Pyridoxal 5′-phosphate (PLP) is an essential cofactor for enzymes in all domains of life. Perturbations in PLP or B(6) vitamer content can be detrimental, notably causing B(6)-dependent epilepsy in humans. YggS homologs are broadly conserved and have been implicated in altered levels of B(6) 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.