The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematode Caenorhabditis elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a C. elegans model of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency.

中文翻译：

---

蛋白质结合的钼辅因子具有生物可利用性，可拯救钼辅因子缺乏的秀丽隐杆线虫

钼辅因子 (Moco) 是一个 520-Da 的修复基团，可在所有生命领域合成。在动物中，四种氧化酶（其中亚硫酸氧化酶）使用 Moco 作为辅基。Moco对动物来说是必不可少的；编码 Moco 生物合成酶的基因发生突变的人类表现出致命的神经和发育缺陷。Moco 补充剂似乎是一种合乎逻辑的疗法。然而，Moco 的不稳定性阻碍了 Moco 转运和生物利用度的生化和细胞生物学研究。线虫Caenorhabditis elegans可以从其细菌食物中摄取 Moco，并将其运输到表达 Moco 所需酶的细胞和组织中，这表明了 Moco 的吸收和分配系统。在这里，我们表明蛋白质结合的 Moco 是稳定的、生物可利用的 Moco 物种，被C. elegans从其饮食中提取，是一种有效的膳食补充剂，可拯救C. Moco缺乏的线虫模型。我们证明了不同的 Moco：蛋白质复合物是稳定的和生物可利用的，这表明了一种生产和递送具有治疗活性的 Moco 来治疗人类 Moco 缺乏症的新策略。