https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&id=37213683&retmode=xml&tool=Litmetric&email=readroberts32@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09 3721368320230523
2662-68101052023MayHorticulture researchHortic ResThe first chromosome-level Fallopia multiflora genome assembly provides insights into stilbene biosynthesis.uhad047uhad047uhad04710.1093/hr/uhad047Fallopia multiflora (Thunb.) Harald, a vine belonging to the Polygonaceae family, is used in traditional medicine. The stilbenes contained in it have significant pharmacological activities in anti-oxidation and anti-aging. This study describes the assembly of the F. multiflora genome and presents its chromosome-level genome sequence containing 1.46 gigabases of data (with a contig N50 of 1.97 megabases), 1.44 gigabases of which was assigned to 11 pseudochromosomes. Comparative genomics confirmed that F. multiflora shared a whole-genome duplication event with Tartary buckwheat and then underwent different transposon evolution after separation. Combining genomics, transcriptomics, and metabolomics data to map a network of associated genes and metabolites, we identified two FmRS genes responsible for the catalysis of one molecule of p-coumaroyl-CoA and three molecules of malonyl-CoA to resveratrol in F. multiflora. These findings not only serve as the basis for revealing the stilbene biosynthetic pathway but will also contribute to the development of tools for increasing the production of bioactive stilbenes through molecular breeding in plants or metabolic engineering in microbes. Moreover, the reference genome of F. multiflora is a useful addition to the genomes of the Polygonaceae family.© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.ZhaoYujiaoYSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei 230012, China.YangZhengyangZSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.ZhangZhongrenZNovogene Bioinformatics Institute, Beijing 301700, China.YinMinzhenMSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.ChuShanshanSSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei 230012, China.TongZhenzhenZSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.QinYuejianYSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.ZhaLiangpingLSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei 230012, China.FangQingyingQSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei 230012, China.YuanYuanYNational Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.HuangLuqiLNational Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.PengHuashengHSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.Research Unit of DAO-DI Herbs, Chinese Academy of Medical Sciences, 2019RU57, Beijing 100700, China.engfigshare10.6084/m9.figshare.19720381Journal Article20230315
EnglandHortic Res1016555402052-7276The authors declare that they have no known conflicts of interest.
202210302023372023522135202352213420235221222023315epublish37213683PMC1019490110.1093/hr/uhad047uhad047Li AR. Fallopia Adans. In: Flora Reipublicae Popularis Sinicae, vol. 25. Science Press: Beijing, 1998.Lin L, Ni B, Lin Het al. . Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: a review. J Ethnopharmacol. 2015;159:158–83.PMC712752125449462C.P. Committee . Pharmacopoeia of P.R. China, Part I. Beijing: China Medical Science and Technology Press; 2020.K.F.D.A. Committee . The Korean Pharmacopoeia. 12th ed. Seoul: The Ministry of Food and Drug Safety Press; 2012.J.P.E. Committee . The Japanese Pharmacopoeia. 17th ed. Tokyo: The Ministry of Health, Labour and Welfare Press; 2016.Zhang L, Yang XH, Deng YY. Evaluation and consideration on safety information abroad of polygonum multiflorum and its preparations. Chin J Chin Mater Med. 2009;34:2414–8.20030101Kim HK, Choi YH, Choi JSet al. . A new stilbene glucoside gallate from the roots of Polygonum multiflorum. Arch Pharm Res. 2008;31:1225–9.18958411Liang L, Xu J, Zhou WWet al. . Integrating targetedand untargeted metabolomics to investigate the processing chemistry of Polygoni Multiflori radix. Front Pharmacol. 2018;9:934.PMC612109330210339Zhao YJ, Chu SS, Gui SYet al. . Tissue-specific metabolite profiling of Fallopia multiflora (Heshouwu) and Fallopia multiflora var. angulata by mass spectrometry imaging and laser microdissection combined with UPLC-Q/TOF-MS. J Pharm Biomed Anal. 2021;200:114070.33878622Wang C, Dai S, Gong Let al. . A review of pharmacology, toxicity and pharmacokinetics of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside. Front Pharmacol. 2022;12:791214.PMC876924135069206Diaz-Gerevini GT, Repossi G, Dain Aet al. . Beneficial action of resveratrol: how and why? Nutrition. 2016;32:174–8.26706021Xia N, Daiber A, Forstermann Uet al. . Antioxidant effects of resveratrol in the cardiovascular system. Br J Pharmacol. 2017;174:1633–46.PMC544657027058985Kiskova T, Kubatka P, Busselberg Det al. . The plant-derived compound resveratrol in brain cancer: a review. Biomol Ther. 2020;10:161–79.PMC702327231963897Austin MB, Noel JP. The chalcone synthase superfamily of type III polyketide synthases. Nat Prod Rep. 2003;20:79–110.12636085Renny-Byfield S, Wendel JF. Doubling down on genomes: polyploidy and crop plants. Am J Bot. 2014;101:1711–25.25090999Panchy N, Lehti-Shiu M, Shiu S-H. Evolution of gene duplication in plants. Plant Physiol. 2016;171:2294–316.PMC497227827288366Dohm JC, Minoche AE, Holtgrawe Det al. . The genome of the recently domesticated crop plant sugar beet (Beta vulgaris). Nature. 2014;505:546–9.24352233Zhang L, Li X, Ma Bet al. . The Tartary buckwheat genome provides insights into Rutin biosynthesis and abiotic stress tolerance. Mol Plant. 2017;10:1224–37.28866080Jiao YN, Wickett NJ, Ayyampalayam Set al. . Ancestral polyploidy in seed plants and angiosperms. Nature. 2011;473:97–100.21478875Christ B, Xu C, Xu Met al. . Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants. Nat Commun. 2019;10:3206.PMC664209331324795Salse J. Ancestors of modern plant crops. Curr Opin Plant Biol. 2016;30:134–42.26985732Vannozzi A, Dry IB, Fasoli Met al. . Genome-wide analysis of the grapevine stilbene synthase multigenic family: genomic organization and expression profiles upon biotic and abiotic stresses. BMC Plant Biol. 2012;12:130.PMC343334722863370Zhao W, Xia WX, Li JWet al. . Transcriptome profiling and digital gene expression analysis of Fallopia multiflora to discover putative genes involved in the biosynthesis of 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside. Gene. 2014;547:126–35.24967942Xia WX, Rui W, Zhao Wet al. . Stable isotope labeling and 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucopyranoside biosynthetic pathway characterization in Fallopia multifora. Planta. 2018;247:613–23.29138972Heath RJ, Rock CO. The Claisen condensation in biology. Nat Prod Rep. 2002;19:581–96.12430724Jeandet P, Delaunois B, Conreux Aet al. . Biosynthesis, metabolism, molecular engineering, and biological functions of stilbene phytoalexins in plants. Biofactors. 2010;36:331–41.20726013Kiselev KV, Grigorchuk VP, Ogneva ZVet al. . Stilbene biosynthesis in the needles of spruce Picea jezoensis. Phytochemistry. 2016;131:57–67.27576046Bowles D, Lim EK, Poppenberger Bet al. . Glycosyltransferases of lipophilic small molecules. Annu Rev Plant Biol. 2006;57:567–97.16669774Yonekura-Sakakibara K, Hanada K. An evolutionary view of functional diversity in family 1 glycosyltransferases. Plant J. 2011;66:182–93.21443631Liu L, Zhou LY, Zhang CRet al. . Cloning and characterization of UDP-L-rhamnose synthase 1/2 from Fallopia multiflora. Acta Pharm Sin. 2019;54:1515–23.Cai QZ, Zhou LY, Liu Let al. . Cloning, bioinformatic, and expression analysis of glycosyltransferase gene from Polygonum multiflorum Thunb. Chin Tradit Herb Drugs. 2021;52:6013–22.Härtl K, Huang FC, Giri APet al. . Glucosylation of smoke-derived volatiles in grapevine (Vitis vinifera) is catalyzed by a promiscuous resveratrol/Guaiacol glucosyltransferase. J Agric Food Chem. 2017;65:5681–9.28656763Maharjan R, Fukuda Y, Shimomura Net al. . An ambidextrous polyphenol glycosyltransferase PaGT2 from Phytolacca americana. Biochemistry. 2020;59:2551–61.32525309Coon MJ. Cytochrome P450: nature's most versatile biological catalyst. Annu Rev Pharmacol Toxicol. 2005;45:1–25.15832443Heitz T, Widemann E, Lugan Ret al. . Cytochromes P450 CYP94C1 and CYP94B3 catalyze two successive oxidation steps of plant hormone jasmonoyl-isoleucine for catabolic turnover. J Biol Chem. 2012;287:6296–306.PMC330733022215670Takahashi S, Yeo YS, Zhao Yet al. . Functional characterization of premnaspirodiene oxygenase, a cytochrome P450 catalyzing regio- and stereo-specific hydroxylations of diverse sesquiterpene substrates. J Biol Chem. 2007;282:31744–54.PMC269536017715131Weitzel C, Simonsen HT. Cytochrome P450-enzymes involved in the biosynthesis of mono- and sesquiterpenes. Phytochem Rev. 2015;14:7–24.Irmler S, Schröder G, St-Pierre Bet al. . Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase. Plant J. 2000;24:797–804.11135113El-Sayed M, Verpoorte R. Catharanthus terpenoid indole alkaloids: biosynthesis and regulation. Phytochem Rev. 2007;6:277–305.Piver B, Fer M, Vitrac Xet al. . Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes. Biochem Pharmacol. 2004;68:773–82.15276085Akashi T, Aoki T, Ayabe S. Cloning and functional expression of a cytochrome P450 cDNA encoding 2-hydroxyisoflavanone synthase involved in biosynthesis of the isoflavonoid skeleton in licorice. Plant Physiol. 1999;121:821–8.PMC5944410557230Beaudoin GA, Facchini PJ. Isolation and characterization of a cDNA encoding (S)-cis-N-methylstylopine 14-hydroxylase from opium poppy, a key enzyme in sanguinarine biosynthesis. Biochem Biophys Res Commun. 2013;431:597–603.23313486Zi J, Peters RJ. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae. Org Biomol Chem. 2013;11:7650–2.PMC392253724108414Dubos C, Stracke R, Grotewold Eet al. . MYB transcription factors in Arabidopsis. Trends Plant Sci. 2010, 2010;15:573–81.20674465Albert NW, Allan AC. MYB genes involved in domestication and crop improvement. Ann Plant Rev. 2021;4:199–242.Alessandro V, Darren CJW, Janine Het al. . Combinatorial regulation of stilbene synthase genes by WRKY and MYB transcription factors in grapevine (Vitis vinifera L.). Plant Cell Physiol. 2018;59:1043–59.29529275Mu H, Li Y, Yuan Let al. . MYB30 and MYB14 form a repressor-activator module with WRKY8 that controls stilbene biosynthesis in grapevine. Plant Cell. 2023;35:552–73.PMC980666136255259Shomura Y, Torayama I, Suh DYet al. . Crystal structure of stilbene synthase from Arachis hypogaea. Proteins. 2005;60:803–6.16028220Yu CK, Springob K, Schmidt Jet al. . A stilbene synthase gene (SbSTS1) is involved in host and nonhost defense responses in sorghum. Plant Physiol. 2005;138:393–401.PMC110419215821144Parage C, Tavares R, Réty Set al. . Structural, functional, and evolutionary analysis of the unusually large stilbene synthase gene family in grapevine. Plant Physiol. 2012;160:1407–19.PMC349060322961129Delaunois B, Cordelier S, Conreux Aet al. . Molecular engineering of resveratrol in plants. Plant Biotechnol J. 2009;7:2–12.19021877Jeandet P, Delaunois B, Aziz Aet al. . Metabolic engineering of yeast and plants for the production of the biologically active Hydroxystilbene, resveratrol. J Biomed Biotechnol. 2012;2012:579089.PMC335982922654481Liu ZY, Zhuang CX, Sheng SJet al. . Overexpression of a resveratrol synthase gene (PcRS) from Polygonum cuspidatum in transgenic Arabidopsis causes the accumulation of trans-piceid with antifungal activity. Plant Cell Rep. 2011;30:2027–36.21717185Wang CH, Zhi S, Liu CYet al. . Characterization of stilbene synthase genes in mulberry (Morus atropurpurea) and metabolic engineering for the production of resveratrol in Escherichia coli. J Agric Food Chem. 2017;65:1659–68.28168876Lee C, Hong WJ, Jung KHet al. . Arachis hypogaea resveratrol synthase 3 alters the expression pattern of UDP-glycosyltransferase genes in developing rice seeds. PLoS One. 2021;16:e0245446.PMC780858833444365Lu D, Zhao W, Xia WXet al. . Cloning, identification of FmSTS2 gene of Fallopia multiflora and the research on relationship between its expression with stilbene Glycoside' expression. Pharm Biotechnol. 2013;20:124–7.Chan EW, Lye PY, Wong SK. Phytochemistry, pharmacology, and clinical trials of Morus alba. Chin J Nat Med. 2016;14:17–30.26850343Li RL, Wang CL, Chen Yet al. . A combined network pharmacology and molecular biology approach to investigate the active ingredients and potential mechanisms of mulberry (Morus alba L.) leaf on obesity. Phytomedicine. 2021;92:153714–25.34508977Pu XD, Li Z, Tian Yet al. . The honeysuckle genome provides insight into the molecular mechanism of carotenoid metabolism underlying dynamic flower coloration. New Phytol. 2020;227:930–43.PMC711622732187685Su X, Zhu ZH, Zhang Let al. . Anti-inflammatory property and functional substances of Lonicerae japonicae caulis. J Ethnopharmacol. 2020;267:113502–15.33189843Han QH, Qian Y, Wang XDet al. . Oleanane-type saponins and prosapogenins from Albizia julibrissin and their cytotoxic activities. Phytochemistry. 2021;185:112674–82.33770687Dubrovina AS, Kiselev KV. Regulation of stilbene biosynthesis in plants. Planta. 2017;246:597–623.28685295Jaillon O, Aury JM, Noel Bet al. . The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla. Nature. 2007;449:463–7.17721507Wang XW, Hu HY, Wu ZJet al. . Tissue-specific transcriptome analyses reveal candidate genes for stilbene, flavonoid and anthraquinone biosynthesis in the medicinal plant Polygonum cuspidatum. BMC Genomics. 2021;22:353–70.PMC812749834000984Serazetdinova L, Oldach KH, Lörz H. Expression of transgenic stilbene synthases in wheat causes the accumulation of unknown stilbene derivatives with antifungal activity. J Plant Physiol. 2005;162:985–1002.16173460Höll J, Vannozzi A, Czemmel Set al. . The R2R3-MYB transcription factors MYB14 and MYB15 regulate stilbene biosynthesis in Vitis vinifera. Plant Cell. 2013;25:4135–49.PMC387779424151295Adrian M, Jeandet P, Douillet-Breuil ACet al. . Stilbene content of mature Vitis vinifera berries in response to UV-C elicitation. J Agric Food Chem. 2000;48:6103–5.11312782Aziz A, Trotel-Aziz P, Dhuicq Let al. . Chitosan oligomers and copper sulfate induce grapevine defense reactions and resistance to gray mold and downy mildew. Phytopathology. 2006;96:1188–94.18943955Guo HL, Luo ZQ, Yang YDet al. . Comparison of stilbene synthase from different plant sources for resveratrol biosynthesis. Chin J Biotech. 2014;30:1622–33.25726587Liu BH, Shi YJ, Yuan JYet al. . Estimation of genomic characteristics by analyzing k-mer frequency in de novo genome projects. Quant Biol. 2013;35:62–7.Zhang QX, Chen WB, Sun LDet al. . The genome of Prunus mume. Nat Commun. 2012;3:187–90.PMC353535923271652Yaffe E, Tanay A. Probabilistic modeling of hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture. Nat Genet. 2011;43:1059–65.22001755Chin CS, Peluso P, Sedlazeck FJet al. . Phased diploid genome assembly with single molecule real-time sequencing. Nat Methods. 2016;13:1050–4.PMC550314427749838Chin CS, Alexander DH, Marks Pet al. . Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nat Methods. 2013;10:563–9.23644548Walker BJ, Abeel T, Shea Tet al. . Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS One. 2014;9:e112963.PMC423734825409509Roach MJ, Schmidt SA, Borneman AR. Purge Haplotigs: allelic contig reassignment for third-gen diploid genome assemblies. BMC Bioinf. 2018;19:460.PMC626703630497373Li H. Toward better understanding of artifacts in variant calling from high-coverage samples. Bioinformatics. 2014;30:2843–51.PMC427105524974202Adey A, Kitzman JO, Burton JNet al. . In vitro, long-range sequence information for de novo genome assembly via transposase contiguity. Genome Res. 2014;24:2041–9.PMC424832025327137Simão FA, Waterhouse RM, Ioannidis Pet al. . BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics. 2017;31:3210–2.26059717Parra G, Bradnam K, Korf I. CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes. Bioinformatics. 2007;23:1061–7.17332020 Hubley R, Smit A. RepeatModeler. http://www.repeatmasker.org/RepeatModeler/.Xu Z, Wang H. LTR_FINDER: an efficient tool for the prediction of full-length LTR retrotransposons. Nucleic Acids Res. 2007;35:W265–8.PMC193320317485477Chen NS. Using RepeatMasker to identify repetitive elements in genomic sequences. Curr Protoc Bioinformatics. 2004;4:10.18428725Altschul SF, Gish W, Miller Wet al. . Basic local alignment search tool. J Mol Biol. 1990;215:403–10.2231712Yu XJ, Zheng HK, Wang Jet al. . Detecting lineage-specific adaptive evolution of brain-expressed genes in human using rhesus macaque as outgroup. Genomics. 2006;88:745–51.16857340Coo KCE, Bergman MT, Cochrane Get al. . The European bioinformatics institute in 2017: data coordination and integration. Nucleic Acids Res. 2018;46:D21–9.PMC575325129186510Kim D, Pertea G, Trapnell Cet al. . TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14:R36.PMC405384423618408Ghosh S, Chan CK. Analysis of RNA-Seq data using TopHat and cufflinks. Methods Mol Biol. 2016;1374:339–61.26519415Haas BJ, Delcher AL, Mount SMet al. . Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies. Nucleic Acids Res. 2003;31:5654–66.PMC20647014500829Burge CB, Karlin S. Finding the genes in genomic DNA. Curr Opin Struct Biol. 1998;8:346–54.9666331Majoros WH, Pertea M, Salzberg SL. TigrScan and GlimmerHMM: two open source ab initio eukaryotic gene-finders. Bioinformatics. 2004;20:2878–9.15145805Blanco E, Parra G, Guigó R. Using geneid to identify genes. Curr Protoc Bioinformatics. 2007;4:4.3.18428791Keller O, Kollmar M, Stanke Met al. . A novel hybrid gene prediction method employing protein multiple sequence alignments. Bioinformatics. 2011;27:757–63.21216780Haas BJ, Salzberg SL, Zhu Wet al. . Automated eukaryotic gene structure annotation using EVidenceModeler and the program to assemble spliced alignments. Genome Biol. 2008;9:R7.PMC239524418190707Altschul SF, Madden TL, Schäffer AAet al. . Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–402.PMC1469179254694Zdobnov EM, Apweiler R. InterProScan--an integration platform for the signature-recognition methods in InterPro. Bioinformatics. 2001;17:847–8.11590104Finn RD, Mistry J, Tate Jet al. . The Pfam protein families database. Nucleic Acids Res. 2010;38:D211–22.PMC280888919920124Finn RD, Clements J, Arndt Wet al. . HMMER web server: 2015 update. Nucleic Acids Res. 2015;43:W30–8.PMC448931525943547Finn RD, Attwood TK, Babbitt PCet al. . InterPro in 2017-beyond protein family and domain annotations. Nucleic Acids Res. 2017;45:D190–9.PMC521057827899635Lowe TM, Eddy SR. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997;25:955–64.PMC1465259023104Nawrocki EP, Kolbe DL, Eddy SR. Infernal 1.0: inference of RNA alignments. Bioinformatics. 2009;25:1335–7.PMC273231219307242Griffithsjones S, Moxon S, Marshall Met al. . Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res. 2005;33:D121–4.PMC54003515608160Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32:1792–7.PMC39033715034147Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30:1312–3.PMC399814424451623Yang ZH. PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol. 2007;24:1586–91.17483113Han MV, Thomas GW, Lugo-Martinez Jet al. . Estimating gene gain and loss rates in the presence of error in genome assembly and annotation using CAFE 3. Mol Biol Evol. 2013;30:1987–97.23709260Tang H, Bowers JE, Wang Xet al. . Synteny and collinearity in plant genomes. Science. 2008;320:486–8.18436778Ellinghaus D, Kurtz S, Willhoeft U. LTRharvest, an efficient and flexible software for de novo detection of LTR retrotransposons. BMC Bioinformatics. 2008;9:18.PMC225351718194517Steinbiss S, Willhoeft U, Gremme Get al. . Fine-grained annotation and classification of de novo predicted LTR retrotransposons. Nucleic Acids Res. 2009;37:7002–13.PMC279088819786494Vilella AJ, Severin J, Ureta-Vidal Aet al. . EnsemblCompara gene trees: complete, duplication-aware phylogenetic trees in vertebrates. Genome Res. 2009;19:327–35.PMC265221519029536