2026-07-21 中国科学院（CAS）
Schematic illustration of the molecular mechanism by which the KCS6-CER2 enzyme complex catalyzes VLCFA elongation in plants. (Image by GIBH)
＜関連情報＞
- https://english.cas.cn/newsroom/research-news/202607/t20260721_1178865.shtml
- https://www.cell.com/molecular-plant/fulltext/S1674-2052(26)00226-1
植物特異的KCS6-CER2複合体の構造解析により、超長鎖脂肪酸の伸長機構が明らかになった Structural snapshots of plant-specific KCS6-CER2 complex reveal the elongation mechanism of very-long-chain fatty acids
Yang Wang ∙ Haiyan Wang ∙ Xianpeng Yang ∙ … ∙ Youwei Xu ∙ Qianmin Wang ∙ Yunjiang Cheng
Molecular Plant Published:July 9, 2026
DOI:https://doi.org/10.1016/j.molp.2026.07.007
Abstract
Very-long-chain fatty acids (VLCFAs) are essential building blocks for sphingolipids, phospholipids, triacylglycerols, suberin, and cuticular waxes, all of which play crucial roles in plant development and environmental adaptation. The elongation of VLCFAs is governed by plant-specific β-ketoacyl-CoA synthase (KCS) enzymes and ECERIFERUM2 (CER2) family proteins. However, the structural catalytic mechanisms underlying VLCFA elongation remain poorly understood. Here, we present structural snapshots of the KCS6-CER2 complex from the evolutionarily representative land vascular plant Selaginella moellendorffii in multiple elongation reaction states. These structures delineate how the acyl chain of the substrate C22:0 acyl-CoA (behenoyl-CoA), the two-carbon donor malonyl-CoA, and the product C24:0 β-ketoacyl-CoA (3-oxo-lignoceroyl-CoA) sequentially engage the subtrate binding channel of the KCS6-CER2 complex on the cytosolic side of the ER membrane. We further identify a previously unrecognized side channel that accommodates an additional acyl-CoA molecule, indicating an unexpected structural feature for VLCFA biosynthesis. In addition, structural and biochemical analyses of the KCS6-CER2 complex reveal that CER2 acts as a structural cofactor, extending the hydrophobic subtrate binding channel of KCS6.Together, these findings uncover the molecular mechanism by which KCS6 and CER2 collaborate to drive chain-length-specific VLCFA elongation and provide a structural framework for understanding and engineering VLCFA elongation across the plant kingdom.
