Novel FAD-dependent uricase produced by food-sourced Priestia megaterium and activity assessment using hyperuricemia Caenorhabditis elegans

IF 8.5 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biological Macromolecules Pub Date : 2025-09-23 DOI:10.1016/j.ijbiomac.2025.147868

Haiyue Chen , Jun Xu , Han Shi, Xinle Liang, Wenjie Wang

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Abstract

The global rise in hyperuricemia (HUA) has driven the quest for safe, non-pharmacological interventions. Food-grade probiotics with HUA-mitigating potential are particularly promising. We isolated a novel strain, SSY-7-2, from traditional fermented wheat pastes, which exhibited robust uric acid (UA) degradation activity. SSY-7-2 showed high average nucleotide identity (ANI) values of 98.76–99.60 % with Priestia megaterium, surpassing the species delineation threshold. Whole-genome sequencing revealed complete UA degradation and purine metabolism pathways. We identified gene SSY_004365 as encoding an FAD-dependent urate hydroxylase (HpmO, E.C. 1.14.13.113), with a Km of 27.36 μM and a Kcat/Km of 5.74 × 10⁴ s⁻¹ M⁻¹. Using UA as the sole nitrogen source, we partially elucidated a conserved HpmO-UraD-HiuH cascade for UA hydrolysis in P. megaterium. Both in vitro and Caenorhabditis elegans models confirmed SSY-7-2's UA degradation activity, safety, and probiotic attributes. These findings expand the bioactivity spectrum of Priestia megaterium and position SSY-7-2 as a promising complementary probiotic for hyperuricemia management.

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由食物来源的巨型线虫产生的新型fad依赖性尿酸酶和使用高尿酸血症的秀丽隐杆线虫活性评估。

全球高尿酸血症（HUA）的上升推动了对安全、非药物干预措施的追求。食品级益生菌具有缓解华化的潜力，尤其有前景。我们从传统发酵小麦膏中分离到一株新的菌株SSY-7-2，该菌株表现出强大的尿酸降解活性。SSY-7-2与巨型Priestia megaterium的平均核苷酸一致性（ANI）值为98.76 ~ 99.60 %，超过了物种划分阈值。全基因组测序揭示了完整的UA降解和嘌呤代谢途径。我们鉴定出SSY_004365基因编码fad依赖性尿酸羟化酶（HpmO， E.C. 1.14.13.113）， Km为27.36 μM， Kcat/Km为5.74 × 104 s-1 M-1。以UA为唯一氮源，我们部分阐明了巨型藻中UA水解的保守HpmO-UraD-HiuH级联。体外和秀丽隐杆线虫模型均证实了SSY-7-2的UA降解活性、安全性和益生菌特性。这些发现扩大了大孢子虫的生物活性谱，并将SSY-7-2定位为一种有前景的高尿酸血症治疗补充益生菌。

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来源期刊

International Journal of Biological Macromolecules 生物-生化与分子生物学

CiteScore

13.70

自引率

9.80%

发文量

2728

审稿时长

64 days

期刊介绍： The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.