Evidence map›Paper›PMID 39090122›Full record

ArticleNature communications2024

Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.

Katherine A Ray, Joshua D Lutgens, Ramesh Bista, Jie Zhang, Ronak R Desai, Melissa Hirsch, Takeshi Miyazawa, Antonio Cordova, Adrian T Keatinge-Clay

Abstract 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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
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  10. Design principles imprinted by evolution.Nature chemical biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Katherine A Ray *Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Joshua D Lutgens *Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Ramesh BistaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Jie ZhangDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Ronak R DesaiDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Melissa HirschDepartment of Chemistry, The University of Texas at Austin, Austin, TX, USA.
Takeshi MiyazawaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Antonio CordovaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.ORCID 0009-0006-0147-5536
Adrian T Keatinge-ClayDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. adriankc@utexas.edu.ORCID 0000-0002-4358-7628

Funding

Harnessing Polyketide Assembly Lines for Medicinal ChemistryR01GM145992 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI KEATINGE-CLAY, ADRIAN TRISTAN · 2022 to 2025
$1.3M
National Science Foundation (NSF) MRSEC Cooperative Agreement No. DMR-1720595NIGMS NIH HHS R01 GM145992U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM145992Welch Foundation F-1712
6 · The paper itself

Abstract

The modular nature of polyketide assembly lines and the significance of their products make them prime targets for combinatorial engineering. The recently updated module boundary has been successful for engineering short synthases, yet larger synthases constructed using the updated boundary have not been investigated. Here we describe our design and implementation of a BioBricks-like platform to rapidly construct 5 triketide, 25 tetraketide, and 125 pentaketide synthases to test every module combination of the pikromycin synthase. Anticipated products are detected from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. We determine ketosynthase gatekeeping and module-skipping are the principal impediments to obtaining functional synthases. The platform is also employed to construct active hybrid synthases by incorporating modules from the erythromycin, spinosyn, and rapamycin assembly lines. The relaxed gatekeeping of a ketosynthase in the rapamycin synthase is especially encouraging in the quest to produce designer polyketides.

Indexed as

MacrolidesPolyketide SynthasesBacterial ProteinsErythromycinPolyketidesProtein EngineeringSirolimusStreptomycesBacterial ProteinsErythromycinMacrolidespicromycinPolyketidesPolyketide SynthasesSirolimus

Identifiers

PMID39090122
PMCPMC11294587

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.