Acyl carrier protein Overview
Acyl carrier protein (ACP) is a small, highly conserved protein that acts as a central scaffold in the biosynthesis of fatty acids and related secondary metabolites, such as polyketides. ACP carries growing acyl chains covalently via a thioester bond to a 4'-phosphopantetheine prosthetic group attached to a conserved serine residue. This transfer and delivery function is essential for the stepwise elongation of fatty acids and assembly of complex natural products. In bacteria and plastids, ACP exists as an independent protein (Type II FAS); in eukaryotic cytosol, ACP is a domain of the large multifunctional Type I fatty acid synthase complex. The structure is a four-helix bundle with conformational flexibility, crucial for its function as an interaction hub for biosynthetic enzymes. Due to its essential role in bacterial viability and secondary metabolism, ACP and its associated pathways are considered attractive targets for new antibiotics and anticancer agents[1][3][5][6].
Mechanism of Action
Inhibition of ACP or ACP-dependent enzymes may block fatty acid biosynthesis in bacteria, inhibiting cell growth and survival[5][7]. Small molecules may disrupt the interaction between ACP and partner enzymes.
Biological Functions
Disease Associations
Safety Considerations
- As ACP is highly conserved in bacteria, plants, and mitochondria of eukaryotes, selective toxicity is a challenge—off-target effects on human or plant fatty acid biosynthesis are safety concerns in drug development[5][7]
- Essentiality to cell metabolism raises risk of toxicity if not targeted specifically in pathogens
Interacting Drugs
Associated Biomarkers
Biomarker |
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Null (no established clinical biomarkers based on ACP status) |