Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria

Chen, Xiaoyue; Hudson, Graham A.; Mineo, Charlotte; Amer, Bashar; Baidoo, Edward E. K.; Crowe, Samantha A.; Liu, Yuzhong; Keasling, Jay D.; Scheller, Henrik V.

doi:10.1038/s41467-023-42877-0

Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria

Journal Article · Sat Nov 04 00:00:00 EDT 2023 · Nature Communications

DOI:https://doi.org/10.1038/s41467-023-42877-0· OSTI ID:2204752

Chen, Xiaoyue; Hudson, Graham A.; Mineo, Charlotte; Amer, Bashar; Baidoo, Edward E. K.; Crowe, Samantha A.; ; ;

Abstract

Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S. vaccaria . This exploration is aided by Pacbio full-length transcriptome sequencing and gene expression analysis. A cellulose synthase-like enzyme can not only glucuronidate triterpenoid aglycones but also alter the product profile of a cytochrome P450 monooxygenase via preference for the aldehyde intermediate. Furthermore, the discovery of a UDP-glucose 4,6-dehydratase and a UDP-4-keto-6-deoxy-glucose reductase reveals the biosynthetic pathway for the rare nucleotide sugar UDP- d -fucose, a likely sugar donor for fucosylation of plant natural products. Our work enables the production and optimization of high-value saponins in microorganisms and plants through synthetic biology approaches.

View Journal Article

Sponsoring Organization:: USDOE

Grant/Contract Number:: NONE; AC02-05CH11231

OSTI ID:: 2204752

Alternate ID(s):: OSTI ID: 2229035

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 14; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (59)

Analysis of bisdesmosidic saponins inSaponaria vaccaria L. by HPLC-PAD-MS: identification of new quillaic acid and gypsogenin 3-O-Trisaccharides Balsevich, J. John; Bishop, Greg G.; Ramirez-Erosa, Irving Phytochemical Analysis, Vol. 17, Issue 6 https://doi.org/10.1002/pca.943	journal	January 2006
Identification of multiple constituents from seed of Vaccaria segetalis with an adsorbent‐separation strategy based on liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry Qi, Peng; Zhang, Feng; Xue, Rui Rapid Communications in Mass Spectrometry, Vol. 28, Issue 11 https://doi.org/10.1002/rcm.6893	journal	April 2014
Synthesis of Uridine 5′-(α-D-Fucopyranosyl Diphosphate) and (Digitoxigenin-3β-yl)-β-D-Fucopyranoside and Enzymatic β-D-Fucosylation of Cardenolide Aglycones in Digitalis lanata1 Faust, T.; Theurer, C.; Eger, K. Bioorganic Chemistry, Vol. 22, Issue 2 https://doi.org/10.1006/bioo.1994.1012	journal	June 1994
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method Livak, Kenneth J.; Schmittgen, Thomas D. Methods, Vol. 25, Issue 4 https://doi.org/10.1006/meth.2001.1262	journal	December 2001
Analysis of transcripts in methyl jasmonate-treated ginseng hairy roots to identify genes involved in the biosynthesis of ginsenosides and other secondary metabolites Choi, Dong-Woog; Jung, JongDuk; Ha, Young Im Plant Cell Reports, Vol. 23, Issue 8 https://doi.org/10.1007/s00299-004-0845-4	journal	November 2004
Adventitious root growth and ginsenoside accumulation in Panax ginseng cultures as affected by methyl jasmonate Kim, Yun-soo; Hahn, Eun-joo; Murthy, Hosakatte Niranjana Biotechnology Letters, Vol. 26, Issue 21 https://doi.org/10.1007/s10529-004-3183-2	journal	November 2004
Amino acid conjugates of jasmonic acid induce jasmonate‐responsive gene expression in barley (Hordeum vulgare L.) leaves No authors listed FEBS Letters, Vol. 414, Issue 2, p. 197-202 https://doi.org/10.1016/S0014-5793(97)01005-3	journal	September 1997
Triterpenoid saponins and sapogenins from Vaccaria segetalis Jia, Zhonghua; Koike, Kazuo; Kudo, Momoe Phytochemistry, Vol. 48, Issue 3 https://doi.org/10.1016/S0031-9422(97)01128-X	journal	June 1998
Plant secondary metabolism linked glycosyltransferases: An update on expanding knowledge and scopes Tiwari, Pragya; Sangwan, Rajender Singh; Sangwan, Neelam S. Biotechnology Advances, Vol. 34, Issue 5 https://doi.org/10.1016/j.biotechadv.2016.03.006	journal	September 2016
Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max Shibuya, Masaaki; Nishimura, Kazuya; Yasuyama, Nao FEBS Letters, Vol. 584, Issue 11 https://doi.org/10.1016/j.febslet.2010.03.037	journal	March 2010
Antiproliferative activity of Saponaria vaccaria constituents and related compounds Balsevich, J. John; Ramirez-Erosa, Irving; Hickie, Robert A. Fitoterapia, Vol. 83, Issue 1 https://doi.org/10.1016/j.fitote.2011.10.010	journal	January 2012
Cultivation of cow cockle (Vaccaria hispanica (Mill.) Rauschert): An industrial–medicinal weed Efthimiadou, Aspasia; Karkanis, Anestis; Bilalis, Dimitrios Industrial Crops and Products, Vol. 40 https://doi.org/10.1016/j.indcrop.2012.03.033	journal	November 2012
Metabolomics driven analysis of Erythrina lysistemon cell suspension culture in response to methyl jasmonate elicitation Farag, Mohamed A.; Mekky, Hattem; El-Masry, Sawsan Journal of Advanced Research, Vol. 7, Issue 5 https://doi.org/10.1016/j.jare.2016.07.002	journal	September 2016
Metabolon formation and metabolic channeling in the biosynthesis of plant natural products Jørgensen, Kirsten; Rasmussen, Anne Vinther; Morant, Marc Current Opinion in Plant Biology, Vol. 8, Issue 3 https://doi.org/10.1016/j.pbi.2005.03.014	journal	June 2005
Biosynthetic diversity in plant triterpene cyclization Phillips, Dereth R.; Rasbery, Jeanne M.; Bartel, Bonnie Current Opinion in Plant Biology, Vol. 9, Issue 3 https://doi.org/10.1016/j.pbi.2006.03.004	journal	June 2006
Segetoside I, a plant-derived bisdesmosidic saponin, induces apoptosis in human hepatoma cells in vitro and inhibits tumor growth in vivo Firempong, Caleb Kesse; Zhang, Hui Yun; Wang, Yan Pharmacological Research, Vol. 110 https://doi.org/10.1016/j.phrs.2016.04.032	journal	August 2016
Methyl jasmonate induced accumulation of kalopanaxsaponin I in Nigella sativa Scholz, Martin; Lipinski, Marta; Leupold, Marco Phytochemistry, Vol. 70, Issue 4 https://doi.org/10.1016/j.phytochem.2009.01.018	journal	March 2009
Transcriptional machineries in jasmonate-elicited plant secondary metabolism De Geyter, Nathan; Gholami, Azra; Goormachtig, Sofie Trends in Plant Science, Vol. 17, Issue 6 https://doi.org/10.1016/j.tplants.2012.03.001	journal	June 2012
A Potent Cancer Vaccine Adjuvant System for Particleization of Short, Synthetic CD8⁺ T Cell Epitopes He, Xuedan; Zhou, Shiqi; Huang, Wei-Chiao ACS Nano, Vol. 15, Issue 3 https://doi.org/10.1021/acsnano.0c07680	journal	February 2021
An Expanded Heterologous GAL Promoter Collection for Diauxie-Inducible Expression in Saccharomyces cerevisiae Peng, Bingyin; Wood, Rebecca J.; Nielsen, Lars K. ACS Synthetic Biology, Vol. 7, Issue 2 https://doi.org/10.1021/acssynbio.7b00355	journal	January 2018
Gene Ontology: tool for the unification of biology Ashburner, Michael; Ball, Catherine A.; Blake, Judith A. Nature Genetics, Vol. 25, Issue 1 https://doi.org/10.1038/75556	journal	May 2000
Long read reference genome-free reconstruction of a full-length transcriptome from Astragalus membranaceus reveals transcript variants involved in bioactive compound biosynthesis Li, Jun; Harata-Lee, Yuka; Denton, Matthew D. Cell Discovery, Vol. 3, Issue 1 https://doi.org/10.1038/celldisc.2017.31	journal	August 2017
JAZ repressor proteins are targets of the SCFCOI1 complex during jasmonate signalling Thines, Bryan; Katsir, Leron; Melotto, Maeli Nature, Vol. 448, Issue 7154 https://doi.org/10.1038/nature05960	journal	July 2007
Folding of xylan onto cellulose fibrils in plant cell walls revealed by solid-state NMR Simmons, Thomas J.; Mortimer, Jenny C.; Bernardinelli, Oigres D. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms13902	journal	December 2016
The ancient CYP716 family is a major contributor to the diversification of eudicot triterpenoid biosynthesis Miettinen, Karel; Pollier, Jacob; Buyst, Dieter Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms14153	journal	February 2017
Salmon provides fast and bias-aware quantification of transcript expression Patro, Rob; Duggal, Geet; Love, Michael I. Nature Methods, Vol. 14, Issue 4 https://doi.org/10.1038/nmeth.4197	journal	March 2017
A cellulose synthase-derived enzyme catalyses 3-O-glucuronosylation in saponin biosynthesis Chung, Soo Yeon; Seki, Hikaru; Fujisawa, Yukiko Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-19399-0	journal	November 2020
Plant terpenoid metabolism co-opts a component of the cell wall biosynthesis machinery Jozwiak, Adam; Sonawane, Prashant D.; Panda, Sayantan Nature Chemical Biology, Vol. 16, Issue 7 https://doi.org/10.1038/s41589-020-0541-x	journal	May 2020
A genomics approach to the early stages of triterpene saponin biosynthesis in Medicago truncatula Suzuki, Hideyuki; Achnine, Lahoucine; Xu, Ran The Plant Journal, Vol. 32, Issue 6 https://doi.org/10.1046/j.1365-313X.2002.01497.x	journal	December 2002
Short-chain dehydrogenase/reductase governs steroidal specialized metabolites structural diversity and toxicity in the genus Solanum Sonawane, Prashant D.; Heinig, Uwe; Panda, Sayantan Proceedings of the National Academy of Sciences, Vol. 115, Issue 23 https://doi.org/10.1073/pnas.1804835115	journal	May 2018
Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques King, Hannah A. D.; Joyce, M. Gordon; Lakhal-Naouar, Ines Proceedings of the National Academy of Sciences, Vol. 118, Issue 38 https://doi.org/10.1073/pnas.2106433118	journal	September 2021
Functional Analysis of Arabidopsis thaliana RHM2/MUM4, a Multidomain Protein Involved in UDP-D-glucose to UDP-L-rhamnose Conversion Oka, Takuji; Nemoto, Tadashi; Jigami, Yoshifumi Journal of Biological Chemistry, Vol. 282, Issue 8 https://doi.org/10.1074/jbc.M610196200	journal	February 2007
Cytotoxic triterpenoid saponins from Vaccaria segetalis Ma, Chun-Hui; Fan, Ming-Song; Lin, Li-Ping Journal of Asian Natural Products Research, Vol. 10, Issue 2 https://doi.org/10.1080/10286020701394381	journal	February 2008
Therapeutic effects of Panax notoginseng saponins in rheumatoid arthritis: network pharmacology and experimental validation Ma, Xinnan; Zhang, Xin; Kong, Yuanhang Bioengineered, Vol. 13, Issue 6 https://doi.org/10.1080/21655979.2022.2086379	journal	June 2022
Adjusting batch effects in microarray expression data using empirical Bayes methods Johnson, W. Evan; Li, Cheng; Rabinovic, Ariel Biostatistics, Vol. 8, Issue 1 https://doi.org/10.1093/biostatistics/kxj037	journal	April 2006
Single-molecule, full-length transcript sequencing provides insight into the extreme metabolism of the ruby-throated hummingbird Archilochus colubris Workman, Rachael E.; Myrka, Alexander M.; Wong, G. William GigaScience, Vol. 7, Issue 3 https://doi.org/10.1093/gigascience/giy009	journal	February 2018
The dTDP-4-dehydro-6-deoxyglucose reductase encoding fcd gene is part of the surface layer glycoprotein glycosylation gene cluster of Geobacillus tepidamans GS5-97T Zayni, Sonja; Steiner, Kerstin; Pföstl, Andreas Glycobiology, Vol. 17, Issue 4 https://doi.org/10.1093/glycob/cwl084	journal	January 2007
The KEGG resource for deciphering the genome Kanehisa, M. Nucleic Acids Research, Vol. 32, Issue 90001 https://doi.org/10.1093/nar/gkh063	journal	January 2004
UniProt: the Universal Protein knowledgebase Apweiler, R. Nucleic Acids Research, Vol. 32, Issue 90001 https://doi.org/10.1093/nar/gkh131	journal	January 2004
limma powers differential expression analyses for RNA-sequencing and microarray studies Ritchie, Matthew E.; Phipson, Belinda; Wu, Di Nucleic Acids Research, Vol. 43, Issue 7 https://doi.org/10.1093/nar/gkv007	journal	January 2015
eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer Nucleic Acids Research, Vol. 44, Issue D1 https://doi.org/10.1093/nar/gkv1248	journal	November 2015
A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae Reider Apel, Amanda; d'Espaux, Leo; Wehrs, Maren Nucleic Acids Research, Vol. 45, Issue 1 https://doi.org/10.1093/nar/gkw1023	journal	November 2016
The Pfam protein families database in 2019 El-Gebali, Sara; Mistry, Jaina; Bateman, Alex Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky995	journal	October 2018
Saponin Biosynthesis in Saponaria vaccaria. cDNAs Encoding β-Amyrin Synthase and a Triterpene Carboxylic Acid Glucosyltransferase Meesapyodsuk, Dauenpen; Balsevich, John; Reed, Darwin W. Plant Physiology, Vol. 143, Issue 2 https://doi.org/10.1104/pp.106.088484	journal	December 2006
Variation in Antiherbivore Defense Responses in Synthetic Nicotiana Allopolyploids Correlates with Changes in Uniparental Patterns of Gene Expression Anssour, Samir; Baldwin, Ian T. Plant Physiology, Vol. 153, Issue 4 https://doi.org/10.1104/pp.110.156786	journal	June 2010
Methyl Jasmonate-Elicited Transcriptional Responses and Pentacyclic Triterpene Biosynthesis in Sweet Basil Misra, Rajesh Chandra; Maiti, Protiti; Chanotiya, Chandan Singh Plant Physiology, Vol. 164, Issue 2 https://doi.org/10.1104/pp.113.232884	journal	December 2013
Use of reverse-phase liquid chromatography, linked to tandem mass spectrometry, to profile the Calvin cycle and other metabolic intermediates in Arabidopsis rosettes at different carbon dioxide concentrations Arrivault, Stéphanie; Guenther, Manuela; Ivakov, Alexander The Plant Journal, Vol. 59, Issue 5 https://doi.org/10.1111/j.1365-313X.2009.03902.x	journal	September 2009
An evolutionary view of functional diversity in family 1 glycosyltransferases Yonekura-Sakakibara, Keiko; Hanada, Kousuke The Plant Journal, Vol. 66, Issue 1 https://doi.org/10.1111/j.1365-313X.2011.04493.x	journal	March 2011
A P450-centric view of plant evolution: P450-centric evolution Nelson, David; Werck-Reichhart, Danièle The Plant Journal, Vol. 66, Issue 1 https://doi.org/10.1111/j.1365-313X.2011.04529.x	journal	March 2011
Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree Reed, James; Orme, Anastasia; El-Demerdash, Amr Science, Vol. 379, Issue 6638 https://doi.org/10.1126/science.adf3727	journal	March 2023
Glycosyltransferases: Structures, Functions, and Mechanisms Lairson, L. L.; Henrissat, B.; Davies, G. J. Annual Review of Biochemistry, Vol. 77, Issue 1 https://doi.org/10.1146/annurev.biochem.76.061005.092322	journal	June 2008
Gene ontology analysis for RNA-seq: accounting for selection bias Young, Matthew D.; Wakefield, Matthew J.; Smyth, Gordon K. Genome Biology, Vol. 11, Issue 2 https://doi.org/10.1186/gb-2010-11-2-r14	journal	January 2010
voom: precision weights unlock linear model analysis tools for RNA-seq read counts Law, Charity W.; Chen, Yunshun; Shi, Wei Genome Biology, Vol. 15, Issue 2 https://doi.org/10.1186/gb-2014-15-2-r29	journal	January 2014
Reconstruction of the full-length transcriptome atlas using PacBio Iso-Seq provides insight into the alternative splicing in Gossypium australe Feng, Shouli; Xu, Min; Liu, Fujie BMC Plant Biology, Vol. 19, Issue 1 https://doi.org/10.1186/s12870-019-1968-7	journal	August 2019
Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives Moses, Tessa; Papadopoulou, Kalliope K.; Osbourn, Anne Critical Reviews in Biochemistry and Molecular Biology, Vol. 49, Issue 6 https://doi.org/10.3109/10409238.2014.953628	journal	October 2014
Differential Gene Expression Analysis in Polygonum minus Leaf upon 24 h of Methyl Jasmonate Elicitation Rahnamaie-Tajadod, Reyhaneh; Loke, Kok-Keong; Goh, Hoe-Han Frontiers in Plant Science, Vol. 8 https://doi.org/10.3389/fpls.2017.00109	journal	February 2017
Isoform Sequencing and State-of-Art Applications for Unravelling Complexity of Plant Transcriptomes An, Dong; Cao, Hieu; Li, Changsheng Genes, Vol. 9, Issue 1 https://doi.org/10.3390/genes9010043	journal	January 2018
Natural and Synthetic Saponins as Vaccine Adjuvants Wang, Pengfei Vaccines, Vol. 9, Issue 3 https://doi.org/10.3390/vaccines9030222	journal	March 2021
Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants Malhotra, Karan; Franke, Jakob Beilstein Journal of Organic Chemistry, Vol. 18 https://doi.org/10.3762/bjoc.18.135	journal	September 2022

Similar Records

Unlocking saponin biosynthesis in soapwort

Journal Article · Tue Jul 23 00:00:00 EDT 2024 · Nature Chemical Biology · OSTI ID:2406092

Cytochrome P450 CYP716A254 catalyzes the formation of oleanolic acid from β-amyrin during oleanane-type triterpenoid saponins biosynthesis in Anemone flaccida

Journal Article · Sun Jan 14 23:00:00 EST 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23134437

Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria

Citation Formats

References (59)

Similar Records

Related Subjects