Evidence map›Paper›PMID 35366417›Full record

ArticleCell2022

Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome.

Jaymin R Patel, Joonseok Oh, Shenqi Wang, Jason M Crawford, Farren J Isaacs

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2022. 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
9.4field-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

23 citing papers in PubMed, 47 citations in OpenAlex.

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  20. Oligonucleotide Catabolism-Derived Gluconucleosides inJournal of the American Chemical Society · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 2 countries.

Jaymin R PatelDepartment of Molecular, Cellular, & Developmental Biology, Yale University, New Haven, CT, USA; Systems Biology Institute, Yale University, West Haven, CT, USA; Institute of Biomolecular Design and Discovery, Yale University, West Haven, CT, USA.
Joonseok OhInstitute of Biomolecular Design and Discovery, Yale University, West Haven, CT, USA; Department of Chemistry, Yale University, New Haven, CT, USA.
Shenqi WangDepartment of Molecular, Cellular, & Developmental Biology, Yale University, New Haven, CT, USA; Systems Biology Institute, Yale University, West Haven, CT, USA.
Jason M CrawfordInstitute of Biomolecular Design and Discovery, Yale University, West Haven, CT, USA; Department of Chemistry, Yale University, New Haven, CT, USA; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, USA. Electronic address: jason.crawford@yale.edu.
Farren J IsaacsDepartment of Molecular, Cellular, & Developmental Biology, Yale University, New Haven, CT, USA; Systems Biology Institute, Yale University, West Haven, CT, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: farren.isaacs@yale.edu.
Yale University · US

Funding

Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
Structural and functional studies of colibactinR01CA215553 · NCI · YALE UNIVERSITY · PI Seth B. Herzon, Christian Jobin · 2018 to 2026
$5.5M
EPA EP-W-17-011NCI NIH HHS R01 CA215553NIGMS NIH HHS T32 GM067543
6 · The paper itself

Abstract

Small molecules encoded by biosynthetic pathways mediate cross-species interactions and harbor untapped potential, which has provided valuable compounds for medicine and biotechnology. Since studying biosynthetic gene clusters in their native context is often difficult, alternative efforts rely on heterologous expression, which is limited by host-specific metabolic capacity and regulation. Here, we describe a computational-experimental technology to redesign genes and their regulatory regions with hybrid elements for cross-species expression in Gram-negative and -positive bacteria and eukaryotes, decoupling biosynthetic capacity from host-range constraints to activate silenced pathways. These synthetic genetic elements enabled the discovery of a class of microbiome-derived nucleotide metabolites-tyrocitabines-from Lactobacillus iners. Tyrocitabines feature a remarkable orthoester-phosphate, inhibit translational activity, and invoke unexpected biosynthetic machinery, including a class of "Amadori synthases" and "abortive" tRNA synthetases. Our approach establishes a general strategy for the redesign, expression, mobilization, and characterization of genetic elements in diverse organisms and communities.

Indexed as

Biosynthetic PathwaysHost Microbial InteractionsMicrobiotaBacteriaEukaryotaGenetic EngineeringHumansMetabolomicsSynthetic Biologycomputer-aided designgenome engineeringmicrobial geneticsnatural productspathway engineeringsecondary metabolismsynthetic biology

Identifiers

PMID35366417
PMCPMC10619838
OpenAlexW4221077803

What OpenQuestion holds

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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.