J Integr Plant Biol. ›› 2023, Vol. 65 ›› Issue (11): 2505-2518.DOI: 10.1111/jipb.13564

• Metabolism and Biochemistry • Previous Articles     Next Articles

Elucidation of the melitidin biosynthesis pathway in pummelo

Shuangqian Shen1†, Shouchuang Wang1†, Chenkun Yang1, Chao Wang1, Qianqian Zhou2, Shen Zhou1, Ran Zhang1, Yufei Li1, Zixuan Wang2, Liupan Dai3, Wenjv Peng2, Yingchen Hao1, Hao Guo1, Guangping Cao1, Xianqing Liu1, Fan Yao3, Qiang Xu4, Alisdair R. Fernie5,6 and Jie Luo1,7*   

  1. 1. Sanya Nanfan Research Institute of Hainan University, Hainan University, Sanya 572025, China;
    2. National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research(Wuhan), Huazhong Agricultural University, Wuhan 430070, China;
    3. Hubei Hongshan Laboratory, College of Life Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan 430070, China;
    4. Key Laboratory of Horticultural Plant Biology of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China;
    5. Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm 14476, Germany;
    6. Centre of Plant Systems Biology and Biotechnology, Plovdiv 4000, Bulgaria;
    7. Yazhouwan National Laboratory, Sanya 572025, China
    These authors contributed equally to this work.
    *Correspondence:Jie Luo(jie.luo@hainanu.edu.cn)
  • Received:2023-05-29 Accepted:2023-09-06 Online:2023-09-07 Published:2023-11-01

Abstract: Specialized plant metabolism is a rich resource of compounds for drug discovery. The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate, but its biosynthetic route in plants has not yet been fully characterized. Here, we describe the gene discovery and functional characterization of a new flavonoid gene cluster (UDP-glucuronosyltransferases (CgUGTs), 1,2 rhamnosyltransferase (Cg1,2RhaT), acyltransferases (CgATs)) that is responsible for melitidin biosynthesis in pummelo (Citrus grandis (L.) Osbeck). Population variation analysis indicated that the tailoring of acyltransferases, specific for bitter substrates, mainly determine the natural abundance of melitidin. Moreover, 3-hydroxy-3-methylglutaryl-CoA reductase enzyme inhibition assays showed that the product from this metabolic gene cluster, melitidin, may be an effective anti-cholesterol statin drug candidate. Co-expression of these clustered genes in Nicotiana benthamiana resulted in the formation of melitidin, demonstrating the potential for metabolic engineering of melitidin in a heterologous plant system. This study establishes a biosynthetic pathway for melitidin, which provides genetic resources for the breeding and genetic improvement of pummelo aimed at fortifying the content of biologically active metabolites.

Key words: bioactive metabolites, biosynthetic pathway, flavonoids, melitidin, natural variation

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