{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ASPDH proteins, which belong to the L‐aspartate dehydrogenase enzyme family, catalyze the reversible conversion between oxaloacetate and L‐aspartate using NAD(P)(H) as a cofactor. In prokaryotic and archaeal systems, these enzymes have been characterized both structurally and kinetically, with some studies demonstrating remarkable thermostability (such as the enzyme from Archaeoglobus, which maintains optimal activity near 80°C even after prolonged incubation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]). Other research has focused on mesophilic homologues—for example, the enzyme from Pseudomonas aeruginosa exhibits high specific activity and versatility with either NAD or NADP as coenzyme, supporting strategies for efficient L‐aspartate production by metabolic engineering ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]. In addition, AspDHs have been implicated in various biosynthetic processes; for instance, an AspDH gene cluster has been associated with the synthesis of polyhydroxyalkanoate precursors, linking aspartate metabolism to carbon and redox flux in the cell ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. Their unique catalytic properties and two‐directional activities not only render them attractive as promising industrial biocatalysts for the production of L‐aspartate and its derivatives under energy‐efficient (anaerobic) conditions ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "], but also underscore their classification as a distinct subgroup within the amino acid dehydrogenase superfamily ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In higher organisms, emerging evidence points to additional regulatory roles for ASPDH. Epigenomic analyses in bovine sperm have revealed that single nucleotide polymorphisms within major quantitative trait loci may affect the methylation status of the ASPDH gene, suggesting a link between its regulation and reproduction traits ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]. Furthermore, in cattle, a de novo nonsense mutation in the ASPDH‐domain–containing gene has been associated with a novel subepidermal vesicular skin disorder, indicating a potential role for ASPDH in maintaining cutaneous integrity ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies support a model in which ASPDH enzymes are central to amino acid metabolism by linking the redox state (via NAD(P)(H) turnover) to carbon flow for both energy generation and biosynthesis. Their intrinsic catalytic versatility not only enables adaptation to extreme environmental conditions but also underpins promising applications in industrial biotechnology while potentially influencing physiological processes and disease phenotypes in multicellular organisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazunari Yoneda, Haruhiko Sakuraba, Hideaki Tsuge, et al. 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