Figure 1: A colored scanning electron micrograph of yeast cells. RIKEN researchers have identified a crucial enzyme that keeps lipid-linked sugar chains in check in yeast cells. © STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY
After a long search, a crucial enzyme for keeping lipid-linked sugar chains in check in yeast cells has been identified by RIKEN researchers1. This finding reveals a novel regulatory mechanism for sugar-donor levels.
Dolichol-linked oligosaccharides (DLOs) are the main sugar donors for a key life process known as N-glycosylation. In this process, oligosaccharides are transferred to asparagine residues on proteins to regulate their stability and function.
"N-glycosylation is a highly conserved modification found across all three domains of life: eukaryotes, bacteria and archaea," explains Tadashi Suzuki of the RIKEN Glycometabolic Biochemistry Laboratory.
Disruptions in this process can lead to serious health conditions in humans, including congenital disorders of glycosylation (CDGs), a group of rare genetic diseases that affect multiple systems in the human body.
Previous studies have shed light on the genes and enzymes involved in DLO biosynthesis. But little was known about how DLOs are degraded.
Some evidence indicated that DLO intermediates are broken down into phosphorylated oligosaccharides (POSs). But the gene encoding DLO-pyrophosphatase, an enzyme responsible for the release of POSs, remained undiscovered.
Now, thanks to the tenacious efforts of Suzuki's group, the search for this elusive enzyme has finally concluded, 15 years after starting the project.
"This has been a particularly challenging project," says Suzuki. "But giving up was not an option; we knew the enzyme exists and were determined to identify the gene."
Suzuki credits his postdoctoral researcher, Sheng-Tao Li, who purified the enzyme. They have named the gene encoding the enzyme as LLP1 after lipid-linked oligosaccharide pyrophosphatase.
The enzyme, Llp1, is located on the membrane of the Golgi body, which is responsible for sorting and directing proteins and lipids to their final location.
They showed that Llp1 targets immature, abnormal and surplus DLOs to break them down into POSs and dolichol phosphate (Dol-P), which is used as a precursor to make new DLOs. By regulating the DLO levels, Llp1 is involved in both quality control and homeostasis of DLO.
"Llp1 is not only degrading DLO; it also promotes the new synthesis of DLO and related compounds," says Suzuki.
Analysis of the Llp1 protein sequence revealed that it belongs to the VanZ-like family of membrane proteins. VanZ genes are found in bacteria resistant to the antibiotic vancomycin, but their function has long puzzled scientists.
"We never expected this," says Suzuki. "This is the beauty of basic science-it can lead to surprising and potentially impactful discoveries."
His team is now focusing on identifying the gene encoding a mammalian counterpart of Llp1, which could illuminate the molecular mechanism underlying some CDGs.
"Our goal is to translate these findings from yeast cells to human health, and to eventually offer new avenues for therapeutic intervention," he says.
Tadashi Suzuki (first row, third from left), Sheng-Tao Li (first row, fourth from left) and co-workers have identified a key enzyme that regulates dolichol-linked oligosaccharides (DLOs) in yeast cells. © 2026 RIKEN
