Evidence map›Paper›PMID 37546965›Full record

ArticleResearch square2023

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

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In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Katherine A RayDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.
Joshua D LutgensDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.
Ramesh BistaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.
Jie ZhangDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.
Ronak R DesaiDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.
Melissa HirschDepartment of Chemistry, The University of Texas at Austin, Austin, TX.
Takeshi MiyazawaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.
Antonio CordovaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.ORCID 0009-0006-0147-5536
Adrian T Keatinge-ClayDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX.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
NIGMS NIH HHS R01 GM145992
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. While short synthases constructed using the recently updated module boundary have been shown to outperform those using the traditional boundary, 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 from the updated modules of the Pikromycin synthase. Every combinatorial possibility of modules 2-6 inserted between the first and last modules of the native synthase was constructed and assayed. Anticipated products were observed from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. Ketosynthase gatekeeping and module-skipping were determined to be the principal impediments to obtaining functional synthases. The platform was also used to create functional hybrid synthases through the incorporation of modules from the Erythromycin, Spinosyn, and Rapamycin assembly lines. The relaxed gatekeeping observed from a ketosynthase in the Rapamycin synthase is especially encouraging in the quest to produce designer polyketides.

Identifiers

PMID37546965
PMCPMC10402262

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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.