2025/09/22 by Xiang Zhang, Jiangbo Xie, Jiadong Wu +4 · 1 voice
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · #Plant Diversity and Evolution #Plant Gene Expression Analysis #Plant Pathogens and Fungal Diseases
paper · pdf · doi:10.1093/hr/uhaf259
openalex publication_date 2025/09/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Abstract Cornus officinalis is a traditional medicinal plant known for producing loganin, a bioactive iridoid glycoside with potential anticancer properties. However, the absence of a high-quality reference genome has limited insights into its biosynthetic pathways. Here, we present a chromosome-level genome assembly of C. officinalis with a size of 2.85 Gb. Comparative genomic analysis revealed that the genome expansion and longer gene structures, relative to other Cornales species, are primarily due to a recent expansion of transposable elements. In this study, we identified unique biosynthetic gene clusters coding multiple core enzymes, including loganin acid O-methyltransferase (LAMT), secologanin synthase (SLS), and cytochrome P450, all of which catalyze sequential steps leading to loganin formation. LAMT enzymes from C. officinalis capable of catalyzing the C-9 hydroxylation of loganin acid were identified, whereas the homolog (CoLMAT) was not found to possess this activity. Additionally, molecular docking studies revealed critical residues in CoLAMT that govern substrate positioning, providing insights into the mechanism of C-9 regioselective hydroxylation. Further characterization of 7-deoxyloganicacid hydroxylase, LAMT, and SLS enzymes allowed us to elucidate the complete biosynthetic pathway of major loganin derivatives in the medicinal plant C. officinalis. Finally, we introduced CoLAMT and its upstream genes into Nicotiana benthamiana and successfully achieved the de novo biosynthesis of a series of loganin derivatives. This work reveals key evolutionary and molecular mechanisms in loganin biosynthesis, providing insights into biotechnological applications in anticancer drug development.