Pseudomonas aeruginosa acyl-CoA dehydrogenases and structure-guided inversion of their substrate specificity

Meng Wang, Prasanthi Medarametla, Thales Kronenberger, Tomas Deingruber, Paul Brear, Wendy Figueroa, Pok-Man Ho, Thomas Krueger, James C. Pearce, Antti Poso, James G. Wakefield, David R. Spring and Martin Welch ()
Additional contact information
Meng Wang: Tennis Court Road
Prasanthi Medarametla: Tennis Court Road
Thales Kronenberger: University of Eastern Finland
Tomas Deingruber: Lensfield Road
Paul Brear: Tennis Court Road
Wendy Figueroa: Tennis Court Road
Pok-Man Ho: Tennis Court Road
Thomas Krueger: Tennis Court Road
James C. Pearce: University of Exeter
Antti Poso: University of Eastern Finland
James G. Wakefield: University of Exeter
David R. Spring: Lensfield Road
Martin Welch: Tennis Court Road

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Fatty acids are a primary source of carbon for Pseudomonas aeruginosa (PA) in the airways of people with cystic fibrosis (CF). Here, we use tandem mass-tag proteomics to analyse the protein expression profile of a CF clinical isolate grown on different fatty acids. Two fatty acyl-CoA dehydrogenases (designated FadE1 and FadE2) are strongly induced during growth on fatty acids. FadE1 displays a strong preference for long-chain acyl-CoAs, whereas FadE2 exclusively utilizes medium-chain acyl-CoAs. Structural analysis of the enzymes enables us to identify residues comprising the substrate selectivity filter in each. Engineering these residues enables us to invert the substrate specificity of each enzyme. Mutants in fadE1 displayed impaired virulence in an infection model, and decreased growth on long chain fatty acids. The unique features of the substrate binding pocket enable us to identify an inhibitor that is differentially active against FadE1 and FadE2.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57532-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57532-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57532-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().