Evidence map›Paper›PMID 36585112›Full record

ArticleJournal of advanced research2023

Identification of oxidosqualene cyclases associated with saponin biosynthesis from Astragalus membranaceus reveals a conserved motif important for catalytic function.

Kuan Chen, Meng Zhang, Lulu Xu, Yang Yi, Linlin Wang, Haotian Wang, Zilong Wang, Jiangtao Xing, Pi Li, Xiaohui Zhang and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal of advanced research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Diverse oxidosqualene cyclases for triterpenoid biosynthesis.Synthetic and systems biotechnology · 2027
    Review
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  11. Research Progress on the Anti-Cancer Effects ofMolecules (Basel, Switzerland) · 2024
    Review
  12. Functional Identification ofInternational journal of molecular sciences · 2024
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  14. MeJA-induced hairy roots inFrontiers in plant science · 2024
    Article
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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

14 authors at 3 institutions in 2 countries.

Kuan ChenState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Meng ZhangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Lulu XuState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Yang YiState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Linlin WangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Haotian WangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Zilong WangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Jiangtao XingThermo Fisher Scientific, Building A, Qiming Plaza, No.101, Wangjing Lize Middle Street, Beijing 100102, China.
Pi LiThermo Fisher Scientific, Building A, Qiming Plaza, No.101, Wangjing Lize Middle Street, Beijing 100102, China.
Xiaohui ZhangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Xiaomeng ShiState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Min YeState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Anne OsbournDepartment of Biochemistry and Metabolism, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom. Electronic address: anne.osbourn@jic.ac.uk.
Xue QiaoState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China; Department of Biochemistry and Metabolism, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom. Electronic address: qiaoxue@bjmu.edu.cn.
Peking University · CNJohn Innes Centre · GBThermo Fisher Scientific (China) · CN

Funding

Biotechnology and Biological Sciences Research Council BBS/E/J/000PR9790
6 · The paper itself

Abstract

introductionTriterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown.

objectivesThis work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus.

methodsTwo OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif.

resultsAmOSC2 is a β-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of β-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for β-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role.

conclusionThe study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Indexed as

SaponinsTriterpenesAstragalus propinquusMolecular Docking SimulationOleanolic AcidPhytosterolsSqualenebeta-amyrincycloartanecycloartenololeananeOleanolic AcidoxidosqualenePhytosterolsSaponinsSqualeneTriterpenesAstragalus membranaceusBiosynthesisConserved motifCycloartenolOxidosqualene cyclase (OSC)β-Amyrin

Identifiers

PMID36585112
PMCPMC9811366
OpenAlexW4221093866

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.