Evidence map›Paper›PMID 31095780›Full record

ArticleThe Plant journal : for cell and molecular biology2019

Functional specialization of UDP-glycosyltransferase 73P12 in licorice to produce a sweet triterpenoid saponin, glycyrrhizin.

Yuhta Nomura, Hikaru Seki, Tomonori Suzuki, Kiyoshi Ohyama, Masaharu Mizutani, Tomomi Kaku, Keita Tamura, Eiichiro Ono, Manabu Horikawa, Hiroshi Sudo and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Plant journal : for cell and molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
9.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 98 citations in OpenAlex.

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  11. Development of phytochemical genomics: From decoding metabolome to functional genomics and biotechnology of plant metabolism.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025
    Review
  12. Article
  13. Article
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  15. Article
  16. Review
  17. The sugar donor specificity of plant family 1 glycosyltransferases.Frontiers in bioengineering and biotechnology · 2024
    Review
  18. Article
  19. Article
  20. Heterologous biosynthesis of medicarpin using engineeredSynthetic and systems biotechnology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 1 country.

Yuhta NomuraDepartment of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Hikaru SekiDepartment of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tomonori SuzukiDepartment of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kiyoshi OhyamaRIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Masaharu MizutaniGraduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo, 657-8501, Japan.
Tomomi KakuDepartment of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Keita TamuraDepartment of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Eiichiro OnoSuntory Global Innovation Center Ltd, Research Institute, 8-1-1 Seikadai, Seika-cho, Soraku-gun, Kyoto, 619-0284, Japan.
Manabu HorikawaSuntory Foundation for Life Sciences, Bioorganic Research Institute, 8-1-1 Seikadai, Seika-cho, Soraku-gun, Kyoto, 619-0284, Japan.
Hiroshi SudoTokiwa Phytochemical Co., Ltd, 158 Kinoko, Sakura, Chiba, 285-0801, Japan.
Hiroaki HayashiSchool of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate, 028-3694, Japan.
Kazuki SaitoRIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Toshiya MuranakaDepartment of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.ORCID 0000-0003-1058-2473
The University of Osaka · JPChiba University · JPRIKEN Center for Sustainable Resource Science · JPIwate Medical University · JPKobe University · JPSuntory Foundation for Life Sciences · JPSuntory (Japan) · JPTokyo Institute of Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glycyrrhizin, a sweet triterpenoid saponin found in the roots and stolons of Glycyrrhiza species (licorice), is an important active ingredient in traditional herbal medicine. We previously identified two cytochrome P450 monooxygenases, CYP88D6 and CYP72A154, that produce an aglycone of glycyrrhizin, glycyrrhetinic acid, in Glycyrrhiza uralensis. The sugar moiety of glycyrrhizin, which is composed of two glucuronic acids, makes it sweet and reduces its side-effects. Here, we report that UDP-glycosyltransferase (UGT) 73P12 catalyzes the second glucuronosylation as the final step of glycyrrhizin biosynthesis in G. uralensis; the UGT73P12 produced glycyrrhizin by transferring a glucuronosyl moiety of UDP-glucuronic acid to glycyrrhetinic acid 3-O-monoglucuronide. We also obtained a natural variant of UGT73P12 from a glycyrrhizin-deficient (83-555) strain of G. uralensis. The natural variant showed loss of specificity for UDP-glucuronic acid and resulted in the production of an alternative saponin, glucoglycyrrhizin. These results are consistent with the chemical phenotype of the 83-555 strain, and suggest the contribution of UGT73P12 to glycyrrhizin biosynthesis in planta. Furthermore, we identified Arg32 as the essential residue of UGT73P12 that provides high specificity for UDP-glucuronic acid. These results strongly suggest the existence of an electrostatic interaction between the positively charged Arg32 and the negatively charged carboxy group of UDP-glucuronic acid. The functional arginine residue and resultant specificity for UDP-glucuronic acid are unique to UGT73P12 in the UGT73P subfamily. Our findings demonstrate the functional specialization of UGT73P12 for glycyrrhizin biosynthesis during divergent evolution, and provide mechanistic insights into UDP-sugar selectivity for the rational engineering of sweet triterpenoid saponins.

Indexed as

ArginineGene Expression Regulation, PlantGlycosyltransferasesGlycyrrhiza uralensisGlycyrrhizic AcidKineticsMolecular Docking SimulationMutationPhylogenyPlant RootsPlants, MedicinalSaponinsTranscriptomeTriterpenesUridine Diphosphate Glucuronic AcidArginineGlycosyltransferasesGlycyrrhizic AcidSaponinsTriterpenesUridine Diphosphate Glucuronic Aciddivergent evolutionfunctional specializationGlycyrrhiza uralensisglycyrrhizinlicoricenatural varianttriterpenoid saponinUDP-glucuronic acidUDP-glycosyltransferase

Identifiers

PMID31095780
PMCPMC6851746
OpenAlexW2946006574

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.