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Synthesis of an acyl-acyl carrier protein synthetase inhibitor to study fatty acid recycling
Journal article   Open access   Peer reviewed

Synthesis of an acyl-acyl carrier protein synthetase inhibitor to study fatty acid recycling

Madeline F. Currie, Dylan M. Persaud, Niralee K. Rana, Amanda J. Platt, Joris Beld and Kara L. Jaremko
Scientific reports, v 10(Oct (E-published)), pp 17776-17776
20 Oct 2020
DOI: https://doi.org/10.1038/s41598-020-74731-4
PMID: 33082446
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/s41598-020-74731-4View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Biochemistry Chemical biology
Fatty acids are essential to most organisms and are made endogenously by the fatty acid synthase (FAS). FAS is an attractive target for antibiotics and many inhibitors are in clinical development. However, some gram-negative bacteria harbor an enzyme known as the acyl-acyl carrier protein synthetase (AasS), which allows them to scavenge fatty acids from the environment and shuttle them into FAS and ultimately lipids. The ability of AasS to recycle fatty acids may help pathogenic gram-negative bacteria circumvent FAS inhibition. We therefore set out to design and synthesize an inhibitor of AasS and test its effectiveness on an AasS enzyme from Vibrio harveyi , the most well studied AasS to date, and from Vibrio cholerae , a pathogenic model. The inhibitor C10-AMS [5′-O-(N-decanylsulfamoyl)adenosine], which mimics the tightly bound acyl-AMP reaction intermediate, was able to effectively inhibit AasS catalytic activity in vitro. Additionally, C10-AMS stopped the ability of Vibrio cholerae to recycle fatty acids from media and survive when its endogenous FAS was inhibited with cerulenin. C10-AMS can be used to study fatty acid recycling in other bacteria as more AasS enzymes continue to be annotated and provides a platform for potential antibiotic development.

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11 citations in Web of Science
10 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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