Evidence map›Paper›PMID 40640164›Full record

ArticleNature communications2025

Phylogenomics and metabolic engineering reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.

Samuel Edward Hakim, Nancy Choudhary, Karan Malhotra, Jian Peng, Arne Bültemeier, Ahmed Arafa, Ronja Friedhoff, Maximilian Bauer, Jessica Eikenberg, Claus-Peter Witte and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
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  10. Review
  11. Subfunctionalization and epigenetic regulation of a biosynthetic gene cluster inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. 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

14 authors.

Samuel Edward Hakim *Institute of Botany, Leibniz University Hannover, 30419, Hannover, Germany.ORCID http://orcid.org/0009-0008-4174-0757
Nancy Choudhary *Institute of Plant Biology & BRICS, TU Braunschweig, 38106, Braunschweig, Germany.ORCID http://orcid.org/0000-0002-2562-7905
Karan Malhotra *Institute of Botany, Leibniz University Hannover, 30419, Hannover, Germany.ORCID http://orcid.org/0000-0002-9748-7067
Jian Peng *Institute of Botany, Leibniz University Hannover, 30419, Hannover, Germany.
Arne Bültemeier *Institute of Botany, Leibniz University Hannover, 30419, Hannover, Germany.ORCID http://orcid.org/0000-0002-7624-5974
Ahmed ArafaInstitute of Botany, Leibniz University Hannover, 30419, Hannover, Germany.ORCID http://orcid.org/0000-0001-5869-4568
Ronja FriedhoffInstitute of Plant Biology & BRICS, TU Braunschweig, 38106, Braunschweig, Germany.ORCID http://orcid.org/0009-0002-0270-4661
Maximilian BauerInstitute of Organic Chemistry, Leibniz University Hannover, 30167, Hannover, Germany.ORCID http://orcid.org/0000-0002-5046-7376
Jessica EikenbergInstitute of Botany, Leibniz University Hannover, 30419, Hannover, Germany.
Claus-Peter WitteDepartment of Molecular Nutrition and Biochemistry of Plants, Leibniz University Hannover, 30419, Hannover, Germany.ORCID http://orcid.org/0000-0002-3617-7807
Marco HerdeDepartment of Molecular Nutrition and Biochemistry of Plants, Leibniz University Hannover, 30419, Hannover, Germany.ORCID http://orcid.org/0000-0003-2804-0613
Philipp HeretschInstitute of Organic Chemistry, Leibniz University Hannover, 30167, Hannover, Germany.ORCID http://orcid.org/0000-0002-9967-3541
Boas PuckerInstitute of Plant Biology & BRICS, TU Braunschweig, 38106, Braunschweig, Germany. pucker@uni-bonn.de.ORCID http://orcid.org/0000-0002-3321-7471
Jakob FrankeInstitute of Botany, Leibniz University Hannover, 30419, Hannover, Germany. jakob.franke@botanik.uni-hannover.de.ORCID http://orcid.org/0000-0002-7603-6232

Funding

Boehringer Ingelheim Stiftung (Boehringer Ingelheim Foundation) Plus 3 Perspectives ProgrammeBundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) de.NBIChina Scholarship Council (CSC) 202208320109Deutsche Forschungsgemeinschaft (German Research Foundation) FR 3720/7-1Deutsche Forschungsgemeinschaft (German Research Foundation) HE7133/8-1Deutsche Forschungsgemeinschaft (German Research Foundation) INST 187/741-1Deutsche Forschungsgemeinschaft (German Research Foundation) PU 718/2-1EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) Consolidator Grant "RadCrossSyn"Ministry of Higher Education (Ministry of Higher Education, Egypt) Call 2019/2020Niedersächsisches Ministerium für Wissenschaft und Kultur (Ministry for Science and Culture of Lower Saxony) SMART BIOTECS
6 · The paper itself

Abstract

Withanolides are steroidal lactones from nightshade (Solanaceae) plants with untapped drug potential due to limited availability of minor representatives caused by lack of biosynthetic pathway knowledge. Here, we combine phylogenomics with metabolic engineering to overcome this limitation. By sequencing the genome of the medicinal plant ashwagandha (Withania somnifera) and comparing it with nine Solanaceae species, we discover a conserved withanolide biosynthesis gene cluster, consisting of two sub gene clusters with differing expression patterns. We establish metabolic engineering platforms in yeast (Saccharomyces cerevisiae) and the model plant Nicotiana benthamiana to reconstitute the first five oxidations of withanolide biosynthesis, catalysed by the cytochrome P450 monooxygenases CYP87G1, CYP88C7, and CYP749B2 and a short-chain dehydrogenase/reductase, producing the aglycone of withanoside V. Enzyme functions are conserved within both sub gene clusters in W. somnifera and between W. somnifera and Physalis pruinosa. Our work sets the basis for biotechnological withanolide production to unlock their pharmaceutical potential.

Indexed as

Metabolic EngineeringMultigene FamilySolanaceaeWithaniaWithanolidesBiosynthetic PathwaysCytochrome P-450 Enzyme SystemGenome, PlantNicotianaPhylogenyPlant ProteinsSaccharomyces cerevisiaeCytochrome P-450 Enzyme SystemPlant ProteinsWithanolides

Identifiers

PMID40640164
PMCPMC12246201

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.