Genetic and Physiological Control of Serine and Glycine Biosynthesis in
            <i>Saccharomyces</i>

Ulane, Rodney E.; Ogur, Maurice

doi:10.1128/jb.109.1.34-43.1972

Cited by 55 publications

(41 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Serine can be used for biosynthesis of glycine, cysteine and tryptophan in many organisms (Pizer, 1965;Ulane and Ogur, 1972;Largen and Belser, 1975;Kitabatake et al, 2000). In the present study, addition of glycine and cysteine, but not tryptophan, enhanced the growth of the crp mutants at levels similar to those observed with addition of serine.…”

Section: Effects Of Crpmt On Growth Of M Tuberculosis and M Bovis Bcgsupporting

confidence: 68%

Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant

Bai

Schaak

Smith

et al. 2011

Molecular Microbiology

View full text Add to dashboard Cite

Summary Mycobacterium tuberculosis CRPMt, encoded by Rv3676 (crp), is a CRP-like transcription factor that binds with the serC – Rv0885 intergenic region. In the present study, we evaluated CRPMt’s regulation of serC and Rv0885 in M. tuberculosis and M. bovis BCG, using site-specific mutagenesis, promoter fusions and RT-PCR. The CRPMt binding site was required for full expression of serC and Rv0885, and expression of both genes was reduced in M. tuberculosis and M. bovis BCG crp mutants. These data show that CRPMt binding directly activates both serC and Rv0885 expression. M. tuberculosis serC restored the ability of an Escherichia coli serC mutant to grow in serine-dropout medium, demonstrating that M. tuberculosis serC encodes a phosphoserine aminotransferase. Serine supplementation, or overexpression of serC, accelerated the growth of M. tuberculosis and M. bovis BCG crp mutants in mycomedium, but not within macrophages. These results establish a role for CRPMt in the regulation of amino acid biosynthesis, and show that reduced serine production contributes to the slow-growth phenotype of M. tuberculosis and M. bovis BCG crp mutants in vitro. Restoration of serine biosynthesis by serC expression will facilitate identification of additional CRPMt-regulated factors required by M. tuberculosis during macrophage and host infection.

show abstract

Section: Effects Of Crpmt On Growth Of M Tuberculosis and M Bovis Bcgsupporting

confidence: 68%

Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant

Bai

Schaak

Smith

et al. 2011

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…In S. cerevisiae, the glycine pathway via Agx1p is repressed by glucose but is the major pathway during growth on nonfermentable carbon sources. Accordingly, the triple deletion mutant gly1 shm1 shm2, which lacks the two alternative glycine pathways, is a glycine auxotroph on glucose (Ulane & Ogur, 1972;Schl€ osser et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A blueprint of the amino acid biosynthesis network of hemiascomycetes

et al. 2014

View full text Add to dashboard Cite

The structure and regulation of biosynthesis pathways in Saccharomyces cerevisiae have been detailed extensively. For other hemiascomycetes, genomic sequences are primarily available, whereas biochemical information on them is scarce. The resulting biochemical networks that are used for research in basic science and biotechnology are often biased by data from S. cerevisiae, assuming that there are often implicitly conserved structures between species. We examined the structure of the amino acid biosynthesis network in nine hemiascomycetes, spanning the phylogenetic clade. Differences in the genetic inventory included the presence and absence of isoenzymes and compartmentation of the pathways. Notably, no two hemiascomycetes had identical genetic inventories. For example, the lack of the mitochondrial αIPMS isoenzyme and presence of only one copy of the BCAA aminotransferase in Pichia pastoris indicate a disparately compartmented leucine biosynthesis pathway. Our findings suggest that αIPMS and BCAA aminotransferase are solely located in the cytosol of P. pastoris, requiring correction of the leucine biosynthesis pathway layout in this species. Our results argue for careful use of information from S. cerevisiae and for joint efforts to fill the knowledge gaps in other species. Such analysis will lead to contributions in biotechnology disciplines, such as protein production and compartment engineering.

show abstract

“…These findings, obtained with the recombinant enzymes in vitro, strongly suggested that the serine depletion observed in the ykl151cD mutant resulted from inhibition of the main serine synthesis pathway at the level of the first dedicated step by the high intracellular NADHX concentrations. As our in vitro results would predict complete inhibition of 3PGA oxidation at the NADHX concentrations reached in the ykl151cD mutant in postdiauxic phase (more than 100-fold higher than the concentrations needed to completely block the Ser33 activity in vitro), the residual serine pool measured in the mutant most likely derived from the glyoxylate route for serine synthesis [36,53]. Discovery of the extremely conserved, but apparently not essential, NAD(P)HX repair system [7] raised the question of its physiological relevance.…”

Section: Nad(p)hx Repair Deficiency Leads To Discrete Changes In Genementioning

confidence: 91%

NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells

et al. 2018

View full text Add to dashboard Cite

NADHX and NADPHX are hydrated and redox inactive forms of the NADH and NADPH cofactors, known to inhibit several dehydrogenases in vitro. A metabolite repair system that is conserved in all domains of life and that comprises the two enzymes NAD(P)HX dehydratase and NAD(P)HX epimerase, allows reconversion of both the S- and R-epimers of NADHX and NADPHX to the normal cofactors. An inherited deficiency in this system has recently been shown to cause severe neurometabolic disease in children. Although evidence for the presence of NAD(P)HX has been obtained in plant and human cells, little is known about the mechanism of formation of these derivatives in vivo and their potential effects on cell metabolism. Here, we show that NAD(P)HX dehydratase deficiency in yeast leads to an important, temperature-dependent NADHX accumulation in quiescent cells with a concomitant depletion of intracellular NAD and serine pools. We demonstrate that NADHX potently inhibits the first step of the serine synthesis pathway in yeast. Human cells deficient in the NAD(P)HX dehydratase also accumulated NADHX and showed decreased viability. In addition, those cells consumed more glucose and produced more lactate, potentially indicating impaired mitochondrial function. Our results provide first insights into how NADHX accumulation affects cellular functions and pave the way for a better understanding of the mechanism(s) underlying the rapid and severe neurodegeneration leading to early death in NADHX repair-deficient children.

show abstract

Genetic and Physiological Control of Serine and Glycine Biosynthesis in Saccharomyces

Cited by 55 publications

References 20 publications

Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant

Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant

A blueprint of the amino acid biosynthesis network of hemiascomycetes

NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells

Contact Info

Product

Resources

About