The biotin-ligating protein BPL-1 is critical for lipid biosynthesis and polarization of the Caenorhabditis elegans embryo

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 bpl-1, which encodes the Caenorhabditis elegans ortholog of HCS. We found that mutations in the biotin-binding region of bpl-1 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 de novo 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 bpl-1 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 C. elegans could help dissect the roles of this important metabolic enzyme under different environmental and dietary conditions.