From the School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington 99164-7520 and.
the Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850.
J Biol Chem. 2018 Jan 12;293(2):610-622. doi: 10.1074/jbc.M117.798553. Epub 2017 Nov 20.
Biotin is an essential cofactor for multiple metabolic reactions catalyzed by carboxylases. Biotin is covalently linked to apoproteins by holocarboxylase synthetase (HCS). Accordingly, some mutations in HCS cause holocarboxylase deficiency, a rare metabolic disorder that can be life-threatening if left untreated. However, the long-term effects of HCS deficiency are poorly understood. Here, we report our investigations of , which encodes the ortholog of HCS. We found that mutations in the biotin-binding region of are maternal-effect lethal and cause defects in embryonic polarity establishment, meiosis, and the integrity of the eggshell permeability barrier. We confirmed that BPL-1 biotinylates four carboxylase enzymes, and we demonstrate that BPL-1 is required for efficient fatty acid biosynthesis. We also show that the lack of larval growth defects as well as nearly normal fatty acid composition in young adult worms is due to sufficient fatty acid precursors provided by dietary bacteria. However, BPL-1 disruption strongly decreased levels of polyunsaturated fatty acids in embryos produced by mutant hermaphrodites, revealing a critical role for BPL-1 in lipid biosynthesis during embryogenesis and demonstrating that dietary fatty acids and lipid precursors are not adequate to support early embryogenesis in the absence of BPL-1. Our findings highlight that studying BPL-1 function in could help dissect the roles of this important metabolic enzyme under different environmental and dietary conditions.
生物素是多种羧化酶催化的代谢反应的必需辅助因子。生物素通过全羧化酶合成酶 (HCS) 与脱辅基蛋白共价结合。因此，HCS 中的一些突变会导致全羧化酶缺乏症，这是一种罕见的代谢紊乱，如果不治疗可能会危及生命。然而，HCS 缺乏的长期影响还知之甚少。在这里，我们报告了对 的研究， 编码 HCS 的 直系同源物。我们发现 中生物素结合区的突变是母体效应致死的，并导致胚胎极性建立、减数分裂和卵壳通透性屏障完整性的缺陷。我们证实 BPL-1 生物素酰化了四种羧化酶，并且我们证明 BPL-1 是有效 脂肪酸生物合成所必需的。我们还表明，幼虫生长缺陷的缺乏以及年轻成年蠕虫中几乎正常的脂肪酸组成是由于饮食细菌提供了足够的脂肪酸前体。然而，BPL-1 缺失强烈降低了 突变体雌雄同体产生的胚胎中多不饱和脂肪酸的水平，这表明 BPL-1 在胚胎发生期间的脂质生物合成中起着关键作用，并表明在缺乏 BPL-1 的情况下，饮食中的脂肪酸和脂质前体不足以支持早期胚胎发生。我们的研究结果强调，研究 中的 BPL-1 功能可以帮助在不同的环境和饮食条件下剖析这种重要代谢酶的作用。
