title: Convergence and divergence of bitterness biosynthesis and regulation in Cucurbitaceae.
abstract: Differentiation of secondary metabolite profiles in closely related plant species provides clues for unravelling biosynthetic pathways and regulatory circuits, an area that is still underinvestigated. Cucurbitacins, a group of bitter and highly oxygenated tetracyclic triterpenes, are mainly produced by the plant family Cucurbitaceae. These compounds have similar structures, but differ in their antitumour activities and ecophysiological roles. By comparative analyses of the genomes of cucumber, melon and watermelon, we uncovered conserved syntenic loci encoding metabolic genes for distinct cucurbitacins. Characterization of the cytochrome P450s (CYPs) identified from these loci enabled us to unveil a novel multi-oxidation CYP for the tailoring of the cucurbitacin core skeleton as well as two other CYPs responsible for the key structural variations among cucurbitacins C, B and E. We also discovered a syntenic gene cluster of transcription factors that regulates the tissue-specific biosynthesis of cucurbitacins and may confer the loss of bitterness phenotypes associated with convergent domestication of wild cucurbits. This study illustrates the potential to exploit comparative genomics to identify enzymes and transcription factors that control the biosynthesis of structurally related yet unique natural products.
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.|Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Science, Shenzhen 518124, China.|Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs (Hunan) Technology Centre, Changsha 410000, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Yongshuo
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs (Hunan) Technology Centre, Changsha 410000, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Institute of Botany, Chinese Academy of Science, Beijing 100093, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Duan
authors.affiliation: Institute of Apiculture Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xue
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Huaisong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.|Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Science, Shenzhen 518124, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: School of Life Science, Shanxi University, Taiyuan 030006, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Peking University Health Science Centre, Beijing 100191, China.
authors.forename: Kewu
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: James
authors.initials: J
authors.lastname: Reed
authors.affiliation: John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Tessa
authors.initials: T
authors.lastname: Moses
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs (Hunan) Technology Centre, Changsha 410000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Qing
authors.affiliation: Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs (Hunan) Technology Centre, Changsha 410000, China.
authors.forename: Xiubin
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Peking University Health Science Centre, Beijing 100191, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
authors.affiliation: College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Hanhui
authors.initials: H
authors.lastname: Kuang
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Osbourn
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary T2N 1N4, Canada.
authors.forename: Dae-Kyun
authors.initials: DK
authors.lastname: Ro
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.|Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Science, Shenzhen 518124, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China.|Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Science, Shenzhen 518124, China.
authors.forename: Sanwen
authors.initials: S
authors.lastname: Huang
mesh_terms: D029773:Citrullus / Q000235:genetics / Q000378:metabolism; D028463:Cucumis melo / Q000235:genetics / Q000378:metabolism; D018553:Cucumis sativus / Q000235:genetics / Q000378:metabolism; D019662:Cucurbitaceae / Q000235:genetics*; D018745:Genome, Plant; D010940:Plant Proteins / Q000096:biosynthesis / Q000235:genetics*; D013045:Species Specificity; D026801:Synteny; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D010940:Plant Proteins; D014157:Transcription Factors