The molybdenum cofactor (Moco) is a 520 dalton prosthetic group that is synthesized in a multi-step enzymatic pathway present in most Archaea, Bacteria, and Eukarya. 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 in a C. elegans model of Moco deficiency. Diverse purified Moco:protein complexes from bacteria, bread mold, green algae, and dairy cows were able to support the growth of otherwise Moco-deficient C. elegans mutants grown on Moco-deficient E. coli. We show that these Moco:protein complexes are very stable, suggesting they may provide a strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency.

中文翻译：

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蛋白质结合的钼辅因子具有生物利用性，可拯救缺乏钼辅因子的秀丽隐杆线虫

钼辅因子（Moco）是一个520道尔顿的辅基，通过大多数古细菌，细菌和Eukarya中存在的多步酶促途径合成。在动物中，有四种氧化酶（包括亚硫酸盐氧化酶）使用Moco作为辅基。Moco对动物至关重要。编码Moco-生物合成酶的基因突变的人类表现出致命的神经和发育缺陷。Moco的补充似乎是一种合乎逻辑的疗法，但是Moco的不稳定性已经排除了Moco转运和生物利用度的生化和细胞生物学研究。线虫秀丽隐杆线虫可以从细菌饮食中摄取Moco，并将其运输到表达Moco所需酶的细胞和组织中，这表明Moco的吸收和分布系统。在这里，我们显示蛋白质结合的Moco是秀丽隐杆线虫从其饮食中摄取的稳定，可生物利用的Moco物种，并且是秀丽隐杆线虫Moco缺乏症模型中的有效膳食补充剂。来自细菌，面包模，绿藻和奶牛的各种纯化的Moco：蛋白质复合物能够支持原本缺乏Moco缺陷的大肠杆菌上生长的缺乏Moco缺陷的秀丽隐杆线虫突变体的生长。我们表明，这些Moco：蛋白复合物非常稳定，表明它们可能为生产和输送具有治疗活性的Moco提供了策略，以治疗人类Moco缺乏症。