Evidence map›Paper›PMID 38360800›Full record

ArticleNature communications2024

Reconstitution of early paclitaxel biosynthetic network.

Jack Chun-Ting Liu, Ricardo De La Peña, Christian Tocol, Elizabeth S Sattely

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
14.5field-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

37 citing papers in PubMed, 63 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Jack Chun-Ting LiuDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3996-5064
Ricardo De La PeñaDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0986-3761
Christian TocolDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA.
Elizabeth S SattelyDepartment of Chemical Engineering, Stanford University, Stanford, CA, USA. sattely@stanford.edu.ORCID 0000-0002-7352-859X
Stanford University · USHoward Hughes Medical Institute · US

Funding

Synthetic biology tools for scalable production of medicinal plant terpenesR01AT010593 · NCCIH · STANFORD UNIVERSITY · PI KEASLING, JAY D, LANGE, BERND MARKUS · 2019 to 2023
$3.5M
NCCIH NIH HHS R01 AT010593
6 · The paper itself

Abstract

Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, we structurally characterize four new products of T5αH, many of which appear to be over-oxidation of the primary mono-oxidized products. By tuning the promoter strength for T5αH expression in Nicotiana plants, we observe decreased levels of these proposed byproducts with a concomitant increase in the accumulation of taxadien-5α-ol, the paclitaxel precursor, by three-fold. This enables the reconstitution of a six step biosynthetic pathway, which we further show may function as a metabolic network. Our result demonstrates that six previously characterized Taxus genes can coordinatively produce key paclitaxel intermediates and serves as a crucial platform for the discovery of the remaining biosynthetic genes.

Indexed as

AlkenesDiterpenesPaclitaxelCytochrome P-450 Enzyme SystemOxidation-ReductionAlkenesCytochrome P-450 Enzyme SystemDiterpenesPaclitaxeltaxa-4(5),11(12)diene

Identifiers

PMID38360800
PMCPMC10869802
OpenAlexW4391836356

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.