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Comparative genomics of the medicinal plants Lonicera macranthoides and L. japonica provides insight into genus genome evolution and hederagenin-based saponin biosynthesis
Authors:Xiaojian Yin  Yaping Xiang  Feng-Qing Huang  Yahui Chen  Hengwu Ding  Jinfa Du  Xiaojie Chen  Xiaoxiao Wang  Xinru Wei  Yuan-Yuan Cai  Wen Gao  Dongshu Guo  Raphael N. Alolga  Xianzhao Kan  Baolong Zhang  Gerardo Alejo-Jacuinde  Ping Li  Lam-Son Phan Tran  Luis Herrera-Estrella  Xu Lu  Lian-Wen Qi
Affiliation:1. Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China;2. Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China

These authors contributed equally to this work.;3. The Institute of Bioinformatics, College of Life Sciences, Anhui Normal University, Wuhu, China;4. Provincial Key Laboratory of Agrobiology, Jiangsu Academy of Agricultural Science, Nanjing, China;5. Institute of Genomics for Crop Abiotic Stress Tolerance, Department of Plant and Soil Science, Texas Tech University, Lubbock, TX, USA

Abstract:Lonicera macranthoides (LM) and L. japonica (LJ) are medicinal plants widely used in treating viral diseases, such as COVID-19. Although the two species are morphologically similar, their secondary metabolite profiles are significantly different. Here, metabolomics analysis showed that LM contained ~86.01 mg/g hederagenin-based saponins, 2000-fold higher than LJ. To gain molecular insights into its secondary metabolite production, a chromosome-level genome of LM was constructed, comprising 9 pseudo-chromosomes with 40 097 protein-encoding genes. Genome evolution analysis showed that LM and LJ were diverged 1.30–2.27 million years ago (MYA). The two plant species experienced a common whole-genome duplication event that occurred ∼53.9–55.2 MYA before speciation. Genes involved in hederagenin-based saponin biosynthesis were arranged in clusters on the chromosomes of LM and they were more highly expressed in LM than in LJ. Among them, oleanolic acid synthase (OAS) and UDP-glycosyltransferase 73 (UGT73) families were much more highly expressed in LM than in LJ. Specifically, LmOAS1 was identified to effectively catalyse the C-28 oxidation of β-Amyrin to form oleanolic acid, the precursor of hederagenin-based saponin. LmUGT73P1 was identified to catalyse cauloside A to produce α-hederin. We further identified the key amino acid residues of LmOAS1 and LmUGT73P1 for their enzymatic activities. Additionally, comparing with collinear genes in LJ, LmOAS1 and LmUGT73P1 had an interesting phenomenon of ‘neighbourhood replication’ in LM genome. Collectively, the genomic resource and candidate genes reported here set the foundation to fully reveal the genome evolution of the Lonicera genus and hederagenin-based saponin biosynthetic pathway.
Keywords:Caprifoliaceae (honeysuckle)  chromosome-level genome  hederagenin-based saponins  Lonicere macranthoides  oleanolic acid synthase  UDP-glycosyltransferase 73P1
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