Evidence map›Paper›PMID 38326309›Full record

ArticleNature communications2024

Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast.

Charlotte Cautereels, Jolien Smets, Peter Bircham, Dries De Ruysscher, Anna Zimmermann, Peter De Rijk, Jan Steensels, Anton Gorkovskiy, Joleen Masschelein, Kevin J Verstrepen

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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

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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 2 institutions in 1 country.

Charlotte CautereelsVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium.
Jolien SmetsVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium.ORCID 0000-0002-2899-4639
Peter BirchamVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium.ORCID 0000-0002-2512-5059
Dries De RuysscherMolecular Biotechnology of Plants and Micro-organisms, Department of Biology, KU Leuven, Kasteelpark Arenberg 31, box 2438, Leuven, 3001, Belgium.
Anna ZimmermannVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium.ORCID 0000-0002-2319-2784
Peter De RijkNeuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, 2610, Belgium.
Jan SteenselsVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium.ORCID 0000-0002-8271-2663
Anton GorkovskiyVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium.ORCID 0000-0003-4811-2282
Joleen MasscheleinMolecular Biotechnology of Plants and Micro-organisms, Department of Biology, KU Leuven, Kasteelpark Arenberg 31, box 2438, Leuven, 3001, Belgium.ORCID 0000-0003-4366-3675
Kevin J VerstrepenVIB Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, Leuven, 3001, Belgium. kevin.verstrepen@kuleuven.be.ORCID 0000-0002-3077-6219
VIB-KU Leuven Center for Microbiology · BEUniversity of Antwerp · BE

Funding

Agentschap Innoveren en Ondernemen (Flanders Innovation & Entrepreneurship) HBC.2020.2623Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders) 12W3918N, 12W3921NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) 1S25923N, 1SC2422NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G019223NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G061821NKU Leuven (Katholieke Universiteit Leuven) C16/17/006
6 · The paper itself

Abstract

Microbes are increasingly employed as cell factories to produce biomolecules. This often involves the expression of complex heterologous biosynthesis pathways in host strains. Achieving maximal product yields and avoiding build-up of (toxic) intermediates requires balanced expression of every pathway gene. However, despite progress in metabolic modeling, the optimization of gene expression still heavily relies on trial-and-error. Here, we report an approach for in vivo, multiplexed Gene Expression Modification by LoxPsym-Cre Recombination (GEMbLeR). GEMbLeR exploits orthogonal LoxPsym sites to independently shuffle promoter and terminator modules at distinct genomic loci. This approach facilitates creation of large strain libraries, in which expression of every pathway gene ranges over 120-fold and each strain harbors a unique expression profile. When applied to the biosynthetic pathway of astaxanthin, an industrially relevant antioxidant, a single round of GEMbLeR improved pathway flux and doubled production titers. Together, this shows that GEMbLeR allows rapid and efficient gene expression optimization in heterologous biosynthetic pathways, offering possibilities for enhancing the performance of microbial cell factories.

Indexed as

RecombinasesSaccharomyces cerevisiaeBiosynthetic PathwaysGene EditingGene ExpressionMetabolic EngineeringRecombinases

Identifiers

PMID38326309
PMCPMC10850122
OpenAlexW4391604696

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.