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Acetohydroxyacid synthase: a target for antimicrobial drug discovery
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia. luke.guddat@uq.edu.au.
Current Pharmaceutical Design
|May 22, 2013
Summary
Acetohydroxyacid synthase (AHAS) is crucial for amino acid synthesis in microbes and plants, making it a target for herbicides. This review explores AHAS inhibitors for potential antimicrobial drug development.
Area of Science:
- Biochemistry
- Enzymology
- Drug Discovery
Background:
- Acetohydroxyacid synthase (AHAS) catalyzes the first step in branched-chain amino acid biosynthesis, a pathway absent in animals.
- AHAS is a validated target for herbicides like sulfonylureas and imidazolinones due to its essential role in microbial and plant metabolism.
Purpose of the Study:
- To review the biochemical characterization of bacterial and fungal AHAS enzymes.
- To analyze structural features critical for AHAS catalysis.
- To present current data on AHAS inhibitors with potential as antimicrobial therapeutics.
Main Methods:
- Biochemical characterization of AHAS from bacterial and fungal sources.
- Structural analysis of AHAS enzymes.
- Review of existing AHAS inhibitor data.
Main Results:
- AHAS requires thiamine diphosphate (ThDP), Mg²⁺, and flavin-adenine dinucleotide (FAD) for activity.
- Commercial herbicides targeting AHAS exhibit high potency and selectivity with low mammalian toxicity.
- Despite its importance, no AHAS inhibitors have been commercialized as antimicrobial agents.
Conclusions:
- AHAS is a promising target for antimicrobial drug development.
- Further research into AHAS inhibitors could lead to novel therapeutics.
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