Evidence map›Paper›PMID 33741955›Full record

ArticleNature communications2021

A computational workflow for the expansion of heterologous biosynthetic pathways to natural product derivatives.

Jasmin Hafner, James Payne, Homa MohammadiPeyhani, Vassily Hatzimanikatis, Christina Smolke

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Review
  2. Article
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  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Deletion of a polyketide synthaseFrontiers in microbiology · 2025
    Article
  11. Article
  12. Applications of synthetic biology in medical and pharmaceutical fields.Signal transduction and targeted therapy · 2023
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Catalytic promiscuity ofHorticulture research · 2022
    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

5 authors.

Jasmin Hafner *Laboratory of Computational Systems Biotechnology, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-1474-5869
James Payne *Department of Bioengineering, Stanford University, Stanford, CA, USA.
Homa MohammadiPeyhaniLaboratory of Computational Systems Biotechnology, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-1308-4659
Vassily HatzimanikatisLaboratory of Computational Systems Biotechnology, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. vassily.hatzimanikatis@epfl.ch.ORCID http://orcid.org/0000-0001-6432-4694
Christina SmolkeDepartment of Bioengineering, Stanford University, Stanford, CA, USA. csmolke@stanford.edu.ORCID http://orcid.org/0000-0002-5449-8495

Funding

Synthetic Biology Platforms for Natural Product Discovery and BiosynthesisDP1AT007886 · NCCIH · STANFORD UNIVERSITY · PI SMOLKE, CHRISTINA D · 2012 to 2016
$3.9M
Enzyme and Pathway Engineering for in vivo Production of Anticancer Noscapine DerivativesF32AT009509 · NCCIH · STANFORD UNIVERSITY · PI PAYNE, JAMES THOMAS · 2017 to 2019
$178k
NCCIH NIH HHS DP1 AT007886NCCIH NIH HHS F32 AT009509
6 · The paper itself

Abstract

Plant natural products (PNPs) and their derivatives are important but underexplored sources of pharmaceutical molecules. To access this untapped potential, the reconstitution of heterologous PNP biosynthesis pathways in engineered microbes provides a valuable starting point to explore and produce novel PNP derivatives. Here, we introduce a computational workflow to systematically screen the biochemical vicinity of a biosynthetic pathway for pharmaceutical compounds that could be produced by derivatizing pathway intermediates. We apply our workflow to the biosynthetic pathway of noscapine, a benzylisoquinoline alkaloid (BIA) with a long history of medicinal use. Our workflow identifies pathways and enzyme candidates for the production of (S)-tetrahydropalmatine, a known analgesic and anxiolytic, and three additional derivatives. We then construct pathways for these compounds in yeast, resulting in platforms for de novo biosynthesis of BIA derivatives and demonstrating the value of cheminformatic tools to predict reactions, pathways, and enzymes in synthetic biology and metabolic engineering.

Indexed as

AlkaloidsBenzylisoquinolinesBiological ProductsBiosynthetic PathwaysComputational BiologyMetabolic EngineeringNoscapinePlantsSaccharomyces cerevisiaeSoftwareAlkaloidsBenzylisoquinolinesBiological ProductsNoscapine

Identifiers

PMID33741955
PMCPMC7979880

What OpenQuestion holds

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LicenceCC BY
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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.