Recombinant Neurospora crassa Saccharopine dehydrogenase [NAD (+), L-lysine-forming] (NCU03118)
Description
Enzymatic Characteristics
Saccharopine dehydrogenase (NAD⁺, L-lysine-forming) (EC 1.5.1.7) catalyzes the oxidative deamination of N⁶-(L-1,3-dicarboxypropyl)-L-lysine (saccharopine) to L-lysine and 2-oxoglutarate, with NAD⁺ serving as a cofactor and H₂O as a reactant .
Key Functions
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Lysine Biosynthesis: Converts saccharopine to lysine in the α-aminoadipic acid pathway .
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Metabolic Regulation: Prevents toxic accumulation of saccharopine, which inhibits glucose-6-phosphate isomerase (GPI) and impairs neuronal development .
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Antifungal Target: Unique to fungi, making it a candidate for antifungal drug development .
Role in Saccharopine Toxicity
Mutations in the SDH domain of α-aminoadipic semialdehyde synthase (AASS) lead to hyperlysinemia-II, characterized by elevated cerebral saccharopine and lysine levels. This results in:
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Impaired Neuronal Development: Saccharopine inhibits GPI’s neurotrophic effects, causing smaller brain size and developmental defects in mice .
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Therapeutic Potential: Exogenous GPI supplementation rescues neuronal defects, highlighting saccharopine degradation as critical for brain development .
| Model | Mutation | Phenotype |
|---|---|---|
| AASS-G489E (SDH) | SDH domain defect | Elevated saccharopine, lysine; defective neurons |
| AASS-R65Q (LKR) | LKR domain defect | Elevated lysine; normal brain development |
Expression and Regulation
In Neurospora crassa, CYS-3 (a transcription factor) upregulates sulfur-responsive genes, including transporters and enzymes for sulfur metabolism. While not directly linked to NCU03118, this underscores interconnected metabolic regulation in fungi .
Recombinant Protein Production
Recombinant NCU07353 (saccharopine dehydrogenase) is commercially available for research:
| Parameter | Details |
|---|---|
| Source | Neurospora crassa |
| Purity | >85% (SDS-PAGE) |
| Applications | Western blotting, ELISA, enzymatic assays |
| Sequence | MVLPGHRLSPSGAKLQPRSLFKREANLDYRYAPEPCRAILTTCRVTSDCCSGMKCVSADGESVCTPSD |
Limitations and Future Directions
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Gene ID Discrepancy: No records for NCU03118 in UniProt, NCBI, or PubMed. Potential causes include:
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Typographical error (e.g., NCU07353).
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Strain-specific nomenclature not publicly documented.
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Structural Gaps: Limited crystallographic data for fungal orthologs beyond PDB 1FF9 .
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Therapeutic Potential: Further studies needed to explore antifungal targets or metabolic modulators .
Product Specs
Note: While we prioritize shipping the format currently in stock, please specify your format preference during order placement for customized preparation.
Note: All proteins are shipped with standard blue ice packs. Dry ice shipping requires advance notice and incurs additional charges.
The tag type is determined during production. If you require a specific tag, please inform us, and we will prioritize its development.
Target Background
This enzyme catalyzes the NAD+-dependent cleavage of saccharopine into L-lysine and 2-oxoglutarate, representing the final step in the α-aminoadipate (AAA) pathway for lysine biosynthesis.
KEGG: ncr:NCU03118
