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Updated: Jun 12, 2025
07:47
Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases
Published on: January 1, 2016
11.5K
Catalytic Redundancies and Conformational Plasticity Drives Selectivity and Promiscuity in Quorum Quenching
Marina Corbella1,2, Joe Bravo3, Andrey O Demkiv2
1Departament de Química Inorgànica (Seeió de Química Orgànica) & Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martíi Franquès 1, 08028 Barcelona, Spain.
JACS Au
|September 27, 2024
Summary
Metallo-β-lactamase-like lactonases (MLLs) can degrade N-acyl L-homoserine lactones (AHLs) involved in microbial quorum sensing. This study reveals MLLs exhibit mechanistic promiscuity, hydrolyzing substrates via multiple pathways, which is key for designing novel quorum quenching enzymes.
Area of Science:
- Biochemistry
- Enzymology
- Microbial Communication
Background:
- Metallo-β-lactamase-like lactonases (MLLs) degrade N-acyl L-homoserine lactones (AHLs), crucial for microbial quorum sensing.
- Quorum sensing contributes to pathogenicity and biofilm formation, making quorum quenching (QQ) enzymes valuable for industrial and biomedical applications.
- Understanding MLL mechanisms and substrate specificities is vital for tailoring QQ enzymes.
Purpose of the Study:
- To conduct a detailed biochemical, computational, and structural study of the MLL GcL.
- To investigate the substrate specificity and catalytic mechanisms of GcL.
- To explore mechanistic promiscuity in MLLs and its implications for enzyme engineering.
Main Methods:
- Biochemical assays to determine enzyme activity and substrate range.
- Computational modeling to analyze enzyme structure and mechanism.
- Structural studies of GcL and related lactonases.
Main Results:
- GcL exhibits broad substrate specificity and hydrolyzes substrates via at least two distinct mechanisms.
- The preferred catalytic mechanism is influenced by substrate structure and active site residues.
- Mechanistic promiscuity is a shared feature among MLLs, including AiiA and AaL, and other enzyme families.
Conclusions:
- MLLs display significant mechanistic promiscuity, a common trait across the family.
- This promiscuity offers opportunities for protein engineering, enabling the design of novel QQ enzymes and other mechanistically versatile enzymes.
- Understanding these mechanisms advances enzyme design for targeted applications in biotechnology and medicine.
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