AI Article Synopsis
- L-serine biosynthesis starts with D-3-phosphoglycerate being converted into 3-phosphohydroxypyruvate by the enzyme SerA, which can also produce D-2-hydroxyglutarate (D-2-HGA) from 2-ketoglutarate.
- Recent discoveries have identified bacterial enzymes called D2HGDHs that convert D-2-HGA back to 2-ketoglutarate; however, little is known about these enzymes in certain bacterial families.
- Two novel D2HGDHs were characterized, revealing their substrate specificity, optimal pH conditions, and sensitivity to metal ions, suggesting their potential use in metabolic engineering for creating microbes with specific traits.
Article Abstract
In and , L-serine biosynthesis is initiated by the action of D-3-phosphoglycerate dehydrogenase (SerA), which converts D-3-phosphoglycerate into 3-phosphohydroxypyruvate. SerA can concomitantly catalyze the production of D-2-hydroxyglutarate (D-2-HGA) from 2-ketoglutarate by oxidizing NADH to NAD. Several bacterial D-2-hydroxyglutarate dehydrogenases (D2HGDHs) have recently been identified, which convert D-2-HGA back to 2-ketoglutarate. However, knowledge about the enzymes that can metabolize D-2-HGA is lacking in bacteria belonging to the family. We found that encodes novel D2HGDHs in and , which were assigned as D2HGDH and D2HGDH, respectively. Inactivation of in and led to the significant accumulation of D-2-HGA. Recombinant D2HGDH and D2HGDH were purified to homogeneity and characterized. D2HGDH and D2HGDH are homotetrameric with a subunit molecular mass of 110 kDa. The pH optimum was 7.5 for D2HGDH and 8.0 for D2HGDH. The Km for D-2-HGA was 208 μM for D2HGDHPa and 83 μM for D2HGDH. The enzymes have strict substrate specificity towards D-2-HGA and displayed maximal activity at 45 °C. Their activity was completely inhibited by 0.5 mM Mn, Ni or Co. The discovery of a novel family of D2HGDHs may provide fundamental information for the metabolic engineering of microbial chassis with desired properties.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504171 | PMC |
| http://dx.doi.org/10.3390/microorganisms10091766 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Brain multi-omic Mendelian randomisation to identify novel drug targets for gliomagenesis.
Hum Mol Genet
November 2024
MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
Background: Genetic variants associated with molecular traits that are also associated with liability to glioma can provide causal evidence for the identification and prioritisation of drug targets.
Methods: We performed comprehensive two-sample Mendelian randomisation (Wald ratio and/or IVW) and colocalisation analyses of molecular traits on glioma. Instrumentable traits (QTLs P < 5 × 10-8) were identified amongst 11 985 gene expression measures, 13 285 splicing isoforms and 10 198 protein abundance measures, derived from 15 brain regions.
Article Synopsis
- Circulating metabolite levels are indicators of human health and can be influenced by genetic factors; however, most research has focused on European populations.
- The study utilized metabolomics data from 25,058 diverse individuals, identifying 1,778 gene loci linked to 667 metabolites and providing methods for data analysis and handling.
- Notably, the research uncovered new genetic associations, including 108 novel gene-metabolite pairs, and highlighted sex differences in metabolism, enhancing the understanding of genetic influences on human health.
Chromosomal translocation resolves a diagnostic odyssey for familial Ruvalcaba syndrome.
Am J Med Genet A
January 2025
Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
In 1971, Ruvalcaba and colleagues reported a new syndrome in two brothers with severe intellectual disability, dysmorphic features, osseous dysplasia, and overlapping features in two intellectually disabled female maternal first cousins. No genetic cause was identified. We report on updated genomic studies and clinical follow-up in this family, including one of the original probands and their niece, whose own lifelong diagnostic odyssey had been unresolved for over four decades.
View Article and Find Full Text PDFA cotton mitochondrial alternative electron transporter, GhD2HGDH, induces early flowering by modulating GA and photoperiodic pathways.
Physiol Plant
June 2024
Institute of Cotton Research, Chinese Academy of Agricultural Sciences, China.
D-2-hydroxyglutarate dehydrogenase (D2HGDH) is a mitochondrial enzyme containing flavin adenine dinucleotide FAD, existing as a dimer, and it facilitates the specific oxidation of D-2HG to 2-oxoglutarate (2-OG), which is a key intermediate in the tricarboxylic acid (TCA) cycle. A Genome-wide expression analysis (GWEA) has indicated an association between GhD2HGDH and flowering time. To further explore the role of GhD2HGDH, we performed a comprehensive investigation encompassing phenotyping, physiology, metabolomics, and transcriptomics in Arabidopsis thaliana plants overexpressing GhD2HGDH.
View Article and Find Full Text PDFIdentification and validation of iron metabolism genes in osteoporosis.
BMC Med Genomics
January 2024
Department of Orthopedic Trauma, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Background: Osteoporosis is the most common metabolic bone disease in humans. Exploring the expression difference of iron metabolism-related genes in osteoporosis can provide a new target for diagnosis and treatment.
Methods: First, we used online databases to identify differentially expressed genes (DEGs) related to iron metabolism in patients with osteoporosis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!