Glycosylation is one of the most prevalent molecular modifications in nature. Single or multiple sugars can decorate a wide range of acceptors from proteins to lipids, cell wall glycans and small molecules, dramatically affecting their activity. Here, we discovered that by ‘hijacking’ an enzyme of the cellulose synthesis machinery involved in cell wall assembly, plants evolved cellulose synthase-like enzymes (Csls) and acquired the capacity to glucuronidate specialized metabolites, that is, triterpenoid saponins. Apparently, endoplasmic reticulum-membrane localization of Csls and of other pathway proteins was part of evolving a new glycosyltransferase function, as plant metabolite glycosyltransferases typically act in the cytosol. Discovery of glucuronic acid transferases across several plant orders uncovered the long-pursued enzymatic reaction in the production of a low-calorie sweetener from licorice roots. Our work opens the way for engineering potent saponins through microbial fermentation and plant-based systems.
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Gene and protein accession numbers can be found in Supplementary Dataset 3. RNA sequencing data have been deposited into the National Center for Biotechnology Information, NIH, Sequence Read Archive (BioProject, PRJNA609035 and accession numbers, SRR11192643-SRR11192647). Source data for Figs. 2 and 3 are provided with the paper.
No custom code or mathematical algorithms were used in this study.
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A.A. is the incumbent of the Peter J. Cohn Professorial Chair. We thank G. Dvir for seeds of studied plants, M. Schuldiner (Weizmann Institute of Science) for plasmids pESC, A. Goossens for standard of medicagenic acid, D. Nelson for CYP nomenclature and M. Court for UGT nomenclature assignment. A.J. received funding from the Dean of Faculty Fellowship. We thank the Adelis Foundation, Leona M. and Harry B. Helmsley Charitable Trust, Jeanne and Joseph Nissim Foundation for Life Sciences, Tom and Sondra Rykoff Family Foundation Research and the Raymond Burton Plant Genome Research Fund for funding and supporting the A.A. laboratory activity.
The authors declare no competing interests.
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Supplementary Figs. 1–46 and Note.
MS based identification of triterpenoid saponins in studied plants.
Transcriptomic data (raw and normalized counts) of spinach samples.
List of primers used in the study.
Coexpression analysis of spinach genes with three baits SOAP1, SOAP2 and CYP716A268v2.
Source data for Supplementary Figures.
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Jozwiak, A., Sonawane, P.D., Panda, S. et al. Plant terpenoid metabolism co-opts a component of the cell wall biosynthesis machinery. Nat Chem Biol 16, 740–748 (2020). https://doi.org/10.1038/s41589-020-0541-x
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