The revised three-step detour pathway in dolichol biosynthesis is evolutionarily conserved in budding yeast

• 成果类型: Article
• 署名作者: Hanaoka, Kazuki; Matsunaga, Kuya; Shimizu, Souichirou; Sakai, Soshi; Pichler, Harald; Funato, Kouichi
• 署名单位: Hiroshima University; Hiroshima University; Graz University of Technology; Austrian Centre of Industrial Biotechnology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2613147123
• 发表日期: 2026-06-02
• 页码: e2613147123
• 关键词: dolichol; congenital disorders of glycosylation (CDGs); TDA5; DHRSX; yeast; CIS-PRENYLTRANSFERASE; glycosylation; disorders; encodes

摘要

The identification of SRD5A3, a causative gene for congenital disorders of glycosylation (CDGs), together with its yeast ortholog DFG10, established the prevailing model that dolichol is synthesized from polyprenol in a single step. Subsequently, a recent discovery of DHRSX in CDG patients revised this view and led to the proposal of a three-step detour pathway for dolichol biosynthesis. However, it remains unclear whether this pathway represents a conserved mechanism or reflects evolutionary diversity in eukaryotes. Here, we identified TDA5 as a yeast ortholog of DHRSX. Deletion of TDA5 caused glycosylation defects, reduced dolichol levels, and accumulated polyprenol. All these phenotypes were rescued by expression of DHRSX, but not by DFG10 or SRD5A3. These findings show that Tda5 serves the same function as DHRSX in yeast, thereby demonstrating conservation of the three-step detour pathway in yeast and supporting a broader eukaryotic framework for dolichol biosynthesis.