Evidence map›Paper›PMID 36088516›Full record

ArticleCommunications biology2022

Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana.

Quentin M Dudley, Seohyun Jo, Delia Ayled Serna Guerrero, Monika Chhetry, Mark A Smedley, Wendy A Harwood, Nathaniel H Sherden, Sarah E O'Connor, Lorenzo Caputi, Nicola J Patron

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
9.3field-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

32 citing papers in PubMed, 73 citations in OpenAlex.

  1. Review
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  8. Metabolic engineering inaBIOTECH · 2025
    Review
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  15. Review
  16. Review
  17. Article
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  19. Article
  20. Cutting-edge plant natural product pathway elucidation.Current opinion in biotechnology · 2024
    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 3 countries.

Quentin M DudleyEngineering Biology, Earlham Institute, Norwich Research Park, Norwich, Norfolk, NR4 7UZ, UK.ORCID 0000-0002-2987-5172
Seohyun JoEngineering Biology, Earlham Institute, Norwich Research Park, Norwich, Norfolk, NR4 7UZ, UK.ORCID 0000-0001-5742-2376
Delia Ayled Serna GuerreroDepartment of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, 07745, Germany.
Monika ChhetryJohn Innes Centre, Norwich Research Park, Norwich, NR4 7TJ, UK.
Mark A SmedleyJohn Innes Centre, Norwich Research Park, Norwich, NR4 7TJ, UK.ORCID 0000-0002-6162-4795
Wendy A HarwoodJohn Innes Centre, Norwich Research Park, Norwich, NR4 7TJ, UK.ORCID 0000-0002-4323-9009
Nathaniel H SherdenJohn Innes Centre, Norwich Research Park, Norwich, NR4 7TJ, UK.
Sarah E O'ConnorDepartment of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, 07745, Germany.ORCID 0000-0003-0356-6213
Lorenzo CaputiDepartment of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, 07745, Germany. lcaputi@ice.mpg.de.
Nicola J PatronEngineering Biology, Earlham Institute, Norwich Research Park, Norwich, Norfolk, NR4 7UZ, UK. nicola.patron@earlham.ac.uk.ORCID 0000-0002-8389-1851
John Innes Centre · GBMax Planck Institute for Chemical Ecology · DENorwich Research Park · GB

Funding

Biotechnology and Biological Sciences Research Council BB/CSP1720/1Biotechnology and Biological Sciences Research Council BB/P010490/1Biotechnology and Biological Sciences Research Council BBS/E/T/000PR9816Biotechnology and Biological Sciences Research Council BBS/E/T/000PR9819
6 · The paper itself

Abstract

Monoterpene indole alkaloids (MIAs) are a diverse class of plant natural products that include a number of medicinally important compounds. We set out to reconstitute the pathway for strictosidine, a key intermediate of all MIAs, from central metabolism in Nicotiana benthamiana. A disadvantage of this host is that its rich background metabolism results in the derivatization of some heterologously produced molecules. Here we use transcriptomic analysis to identify glycosyltransferases that are upregulated in response to biosynthetic intermediates and produce plant lines with targeted mutations in the genes encoding them. Expression of the early MIA pathway in these lines produces a more favorable product profile. Strictosidine biosynthesis was successfully reconstituted, with the best yields obtained by the co-expression of 14 enzymes, of which a major latex protein-like enzyme (MLPL) from Nepeta (catmint) is critical for improving flux through the iridoid pathway. The removal of endogenous glycosyltransferases does not impact the yields of strictosidine, highlighting that the metabolic flux of the pathway enzymes to a stable biosynthetic intermediate minimizes the need to engineer the endogenous metabolism of the host. The production of strictosidine in planta expands the range of MIA products amenable to biological synthesis.

Indexed as

MonoterpenesNicotianaGlycosyltransferasesIndole AlkaloidsPlantsGlycosyltransferasesIndole AlkaloidsMonoterpenes

Identifiers

PMID36088516
PMCPMC9464250
OpenAlexW4295113676

What OpenQuestion 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 OpenQuestion graph.