Evidence map›Paper›PMID 33384421›Full record

ArticleHorticulture research2021

The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila.

Xiaolong Hao, Chenhong Xie, Qingyan Ruan, Xichen Zhang, Chao Wu, Bing Han, Jun Qian, Wei Zhou, Hans-Wilhelm Nützmann, Guoyin Kai

Open access · goldAbstract read
In one paragraph

Article in Horticulture research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Biotechnological approaches for the production of camptothecin.Applied microbiology and biotechnology · 2024
    Review
  9. Genome-Wide Identification and Expression Analysis of WRKY Gene Family inInternational journal of molecular sciences · 2023
    Article
  10. Article
  11. Profiles of Metabolic Genes inBiomolecules · 2022
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Functional analysis ofFrontiers in plant science · 2022
    Article
  19. Review
  20. Review
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

10 authors at 3 institutions in 2 countries.

Xiaolong HaoLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Chenhong XieLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Qingyan RuanLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Xichen ZhangInstitute of Plant Biotechnology, School of Life Sciences, Shanghai Normal University, 200234, Shanghai, China.
Chao WuInstitute of Plant Biotechnology, School of Life Sciences, Shanghai Normal University, 200234, Shanghai, China.
Bing HanLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Jun QianLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Wei ZhouLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Hans-Wilhelm NützmannThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Guoyin KaiLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, 310053, Hangzhou, China. kaiguoyin@163.com.ORCID http://orcid.org/0000-0001-7586-9067
Zhejiang Chinese Medical University · CNShanghai Normal University · CNUniversity of Bath · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The limited bioavailability of plant-derived natural products with anticancer activity poses major challenges to the pharmaceutical industry. An example of this is camptothecin, a monoterpene indole alkaloid with potent anticancer activity that is extracted at very low concentrations from woody plants. Recently, camptothecin biosynthesis has been shown to become biotechnologically amenable in hairy-root systems of the natural producer Ophiorrhiza pumila. Here, time-course expression and metabolite analyses were performed to identify novel transcriptional regulators of camptothecin biosynthesis in O. pumila. It is shown here that camptothecin production increased over cultivation time and that the expression pattern of the WRKY transcription factor encoding gene OpWRKY2 is closely correlated with camptothecin accumulation. Overexpression of OpWRKY2 led to a more than three-fold increase in camptothecin levels. Accordingly, silencing of OpWRKY2 correlated with decreased camptothecin levels in the plant. Further detailed molecular characterization by electrophoretic mobility shift, yeast one-hybrid and dual-luciferase assays showed that OpWRKY2 directly binds and activates the central camptothecin pathway gene OpTDC. Taken together, the results of this study demonstrate that OpWRKY2 acts as a direct positive regulator of camptothecin biosynthesis. As such, a feasible strategy for the over-accumulation of camptothecin in a biotechnologically amenable system is presented.

Identifiers

PMID33384421
PMCPMC7775441
OpenAlexW3116828610

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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.