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Jo, Seohyun, El-Demerdash, Amr 
ORCID: https://orcid.org/0000-0001-6459-2955, Owen, Charlotte, Srivastava, Vikas, Wu, Dewei, Kikuchi, Shingo, Reed, James, Hodgson, Hannah, Harkess, Alex, Shu, Shengqiang, Plott, Chris, Jenkins, Jerry, Williams, Melissa, Boston, Lori-Beth, Lacchini, Elia, Qu, Tongtong, Goossens, Alain, Grimwood, Jane, Schmutz, Jeremy, Leebens-Mack, Jim and Osbourn, Anne
(2024)
Unlocking saponin biosynthesis in soapwort.
Nature Chemical Biology.
ISSN 1552-4450
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Abstract
Soapwort (Saponaria officinalis) is a flowering plant from the Caryophyllaceae family with a long history of human use as a traditional source of soap. Its detergent properties are because of the production of polar compounds (saponins), of which the oleanane-based triterpenoid saponins, saponariosides A and B, are the major components. Soapwort saponins have anticancer properties and are also of interest as endosomal escape enhancers for targeted tumor therapies. Intriguingly, these saponins share common structural features with the vaccine adjuvant QS-21 and, thus, represent a potential alternative supply of saponin adjuvant precursors. Here, we sequence the S. officinalis genome and, through genome mining and combinatorial expression, identify 14 enzymes that complete the biosynthetic pathway to saponarioside B. These enzymes include a noncanonical cytosolic GH1 (glycoside hydrolase family 1) transglycosidase required for the addition of d-quinovose. Our results open avenues for accessing and engineering natural and new-to-nature pharmaceuticals, drug delivery agents and potential immunostimulants.
| Item Type: | Article |
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| Additional Information: | Data availability statement: The fully assembled and annotated S. officinalis genome sequence was deposited under BioProject ID PRJNA1018723. The RNA-seq reads were deposited under BioProject IDs PRJNA1008697 and PRJNA1035542. The sequences of the genes characterized in this study can also be found in GenBank as follows: SobAS1 (OR426407), CYP716A378 (OR426395), CYP716A379 (OR426402), CYP72A984 (OR426401), SoCSL1 (OR426404), UGT73DL1 (OR426405), UGT73CC6 (OR426403), SoSDR1 (OR426396), UGT74CD1 (OR426399), UGT79T1 (OR426408), UGT79L3 (OR426397), UGT73M2 (OR426400), SoGH1 (OR426398) and SoBAHD1 (OR426406). The InterPro-85.0 (https://www.ebi.ac.uk/interpro/) and Pfam-33.1 (http://pfam.xfam.org/) databases were also consulted. The data that support the findings of this study are available within the main text and the Supplementary Information. Data are also available from the corresponding author upon request. Source data are provided with this paper. Funding information: This work was supported by the Biotechnological and Biological Sciences Research Council (BBSRC) Super Follow-on-Fund award (BB/W017857/1 to S.J., BB/V015176/1 to A.E-D. and BB/T015063/1 to H.H.), a Royal Society Newton International Fellowship (NIF\R1\211270 to V.S.), a CEPAMS award (to D.W.), the NIH (RO1 AT010593-01 to J.R.), the BBRSC Institute Strategic Program Grant ‘Harnessing biosynthesis for sustainable food and health’ (BB/X01097X/1) and the John Innes Foundation (to S.J., C.O. and A.O.). We thank JIC horticultural services for assistance with plant cultivation, the JIC metabolomics, NMR and chemistry platforms for assistance with instruments and method development, the Norwich Bioscience Institutes (NBI) Research Computing for computational support and the Earlham Institute (EI) for sequencing of the S. officinalis transcriptome. The work (proposal: https://doi.org/10.46936/10.25585/60001405) conducted by the US Department of Energy (DOE) Joint Genome Institute (https://ror.org/04xm1d337), a DOE Office of Science User Facility, is supported by the Office of Science of the US DOE operated under contract no. DE-AC02-05CH11231. We also thank D. Nelson and the UGT Nomenclature Committee for formal assignment of the S. officinalis CYPs and UGTs, respectively. |
| Uncontrolled Keywords: | molecular biology,cell biology,sdg 3 - good health and well-being,4* ,/dk/atira/pure/subjectarea/asjc/1300/1312 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Science > School of Pharmacy (former - to 2024) |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 02 Aug 2024 08:30 |
| Last Modified: | 08 Aug 2024 08:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96108 |
| DOI: | 10.1038/s41589-024-01681-7 |
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