GO:0004313 [acyl-carrier-protein] S-acetyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0004313 describes the enzymatic transfer of an acetyl group from acetyl-CoA to an acyl-carrier protein (ACP), producing acetyl-ACP and free CoA.
• This activity is a gatekeeping step in fatty acid biosynthesis, supplying the primer unit for de novo lipogenesis.
• The reaction is catalyzed by dedicated acetyltransferases and by the acetyltransferase domain of multifunctional type I fatty acid synthases (FASN).
• Dysregulation of acetyl-ACP formation is linked to cancer, immune cell exhaustion, and metabolic disorders.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of GO:0004313 in disease.
• Combining CRISPR screening with lipidomics and transcriptomics is a powerful strategy to identify regulators of this activity.
Description
GO:0004313, [acyl-carrier-protein] S-acetyltransferase activity, is a molecular function that catalyzes the transfer of an acetyl group from acetyl-coenzyme A (acetyl-CoA) to an acyl-carrier protein (ACP), yielding acetyl-ACP and coenzyme A. This reaction is the first committed step in fatty acid biosynthesis, providing the two-carbon primer that is subsequently elongated by ketoacyl synthases. Because acetyl-ACP formation determines the rate and specificity of de novo lipogenesis, its regulation is central to cellular lipid homeostasis. In cancer, upregulated fatty acid synthesis supports membrane biogenesis and signaling, and acetyltransferase activity is often elevated. In immune cells, lipid metabolism reprogramming driven by acetyltransferase-dependent pathways influences T cell exhaustion and regulatory T cell function. Consequently, researchers study GO:0004313 to understand how cells allocate acetyl-CoA between energy production, acetylation, and membrane synthesis. This article integrates the QuickGO definition with verified PubMed literature to outline the mechanism, key genes, disease links, and CRISPR-based research methods for GO:0004313.
[acyl-carrier-protein] S-acetyltransferase activity At A Glance
| GO ID | GO:0004313 |
|---|---|
| GO term | [acyl-carrier-protein] S-acetyltransferase activity |
| Ontology | molecular_function |
| Synonym | ACAT activity; acetyl-CoA:acyl-carrier-protein S-acetyltransferase activity; ACP S-acetyltransferase activity; acyl-carrier-protein acetyltransferase activity |
| Major function | Transfer of acetyl group from acetyl-CoA to acyl-carrier protein, initiating fatty acid biosynthesis |
| Reaction | acetyl-CoA + [acyl-carrier protein] = CoA + acetyl-[acyl-carrier protein] |
| Related pathways | Fatty acid biosynthesis, lipid metabolism, acetyl-CoA homeostasis |
| Cellular context | Cytosol, mitochondria, and plastids depending on organism |
| Disease relevance | Cancer, immune exhaustion, metabolic disorders, osteoarthritis |
What Is GO:0004313?
According to QuickGO, GO:0004313 is defined as the catalysis of the reaction: acetyl-CoA + [acyl-carrier protein] = CoA + acetyl-[acyl-carrier protein]. In other words, it is an acetyltransferase that loads an acetyl group onto the phosphopantetheine arm of an acyl-carrier protein, priming it for fatty acid chain elongation.
Why Is [acyl-carrier-protein] S-acetyltransferase activity Important in Cell Biology?
GO:0004313 is important because it controls the entry of acetyl units into the fatty acid synthesis pathway, thereby influencing membrane lipid composition, energy storage, and signaling lipid production. Dysregulation of this activity contributes to cancer progression, immune cell dysfunction, and metabolic diseases, making it a potential therapeutic target.
• Initiates de novo fatty acid synthesis by providing acetyl-ACP primer.
• Regulates lipid metabolism reprogramming in cancer cells.
• Modulates T cell exhaustion and anti-PD-1 resistance in hepatocellular carcinoma.
• Supports regulatory T cell functional specialization in tumors.
• Links acetyl-CoA pools to histone acetylation and gene expression.
• Involved in COVID-19-associated lipid metabolism alterations.
• Contributes to osteoarthritis-related cholesterol metabolism changes.
• Target for autophagy modulation via FASN-dependent pathways.
• Potential biomarker for ferroptosis suppression in ovarian cancer.
• Enables CRISPR-based functional genomics of lipid metabolism.
What Happens During [acyl-carrier-protein] S-acetyltransferase activity?
Acetyl-CoA binding and acyl-carrier protein recognition
In simple terms: The enzyme grabs an acetyl group from acetyl-CoA and holds it ready to attach to a carrier protein.
The acetyltransferase domain binds acetyl-CoA and positions the acetyl group for transfer to the phosphopantetheine arm of the acyl-carrier protein (ACP). This step is highly specific and requires the ACP to be post-translationally modified with a 4'-phosphopantetheine prosthetic group.
Acetyl transfer and acetyl-ACP formation
In simple terms: The acetyl group is handed off to the carrier protein, forming acetyl-ACP.
Catalysis proceeds via a ping-pong mechanism in which the acetyl group is transiently attached to a catalytic cysteine or serine residue before being transferred to the ACP. The product, acetyl-ACP, serves as the primer for subsequent condensation reactions by ketoacyl synthase.
Release of coenzyme A and recycling
In simple terms: CoA is released and the enzyme is ready for another round.
After acetyl transfer, coenzyme A is released, and the enzyme returns to its resting state to catalyze another cycle. The acetyl-ACP then enters the elongation cycle of fatty acid synthesis, where it is extended by two-carbon units.
Integration with fatty acid synthase complex
In simple terms: In some organisms, this activity is part of a larger fatty acid factory.
In type I fatty acid synthases, the acetyltransferase activity resides within a multifunctional polypeptide, coordinating with other catalytic domains to ensure efficient substrate channeling. In type II systems, it is a standalone enzyme that interacts with ACP and other components.
Key Genes Involved in GO:0004313 [acyl-carrier-protein] S-acetyltransferase activity
The following genes and proteins are directly or indirectly involved in GO:0004313, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FASN | Multifunctional enzyme with acetyltransferase domain; catalyzes acetyl transfer to ACP | Target in cancer, autophagy, and ferroptosis studies |
| ACACA | Acetyl-CoA carboxylase; supplies malonyl-CoA for elongation | Regulates lipid synthesis and is linked to metabolic disorders |
| ACACB | Acetyl-CoA carboxylase beta; controls fatty acid oxidation | Potential target in obesity and diabetes |
| MCAT | Malonyl-CoA-acyl carrier protein transacylase; transfers malonyl to ACP | Mitochondrial fatty acid synthesis component |
| OXSM | 3-oxoacyl-ACP synthase; elongates acetyl-ACP | Mitochondrial fatty acid synthesis |
| CBR4 | Carbonyl reductase 4; involved in fatty acid synthesis | Associated with lipid metabolism |
| HSD17B8 | Hydroxysteroid 17-beta dehydrogenase 8; part of mitochondrial FAS | Linked to metabolic regulation |
| PPT1 | Palmitoyl-protein thioesterase 1; affects lipid modification | Neurodegeneration and lipid metabolism |
| SLC7A11 | Cystine/glutamate antiporter; linked to ferroptosis and FASN | Ovarian cancer and ferroptosis suppression |
| USP43 | Deubiquitinase that stabilizes FASN | Ovarian cancer progression |
| YY1 | Transcription factor inducing USP43 | Regulates FASN stability |
| Riplet | E3 ligase promoting lipid metabolism changes | CD8 T cell exhaustion in HCC |
| PD-1 | Immune checkpoint; resistance linked to lipid metabolism | Anti-PD-1 therapy in HCC |
| mTOR | Kinase regulating lipid synthesis | Treg functional specialization |
| SREBP1 | Transcription factor controlling lipogenic genes | Regulates FASN expression |
| PPARγ | Nuclear receptor regulating lipid metabolism | Involved in osteoarthritis and cholesterol metabolism |
| IL-10 | Cytokine influencing Treg lipid metabolism | Tumor immune regulation |
| TGF-β | Cytokine linked to lipid signaling in Tregs | Tumor microenvironment |
How Is [acyl-carrier-protein] S-acetyltransferase activity Regulated?
GO:0004313 is regulated at multiple levels. Transcriptionally, SREBP1 and PPARγ control the expression of FASN and other lipogenic genes. Post-translationally, FASN stability is regulated by ubiquitination and deubiquitination, for example via USP43. Signaling pathways such as mTOR and AMPK modulate acetyltransferase activity in response to nutrient availability. Additionally, lactylation of FASN can inhibit its activity, linking metabolic state to enzyme function.
[acyl-carrier-protein] S-acetyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FASN | Ovarian cancer, ferroptosis suppression | FASN knockout ovarian cancer cell lines |
| Riplet | Hepatocellular carcinoma, CD8 T cell exhaustion | Riplet knockout mouse models |
| mTOR | Treg functional specialization in tumors | mTOR conditional knockout mice |
| USP43 | Ovarian cancer progression | USP43 overexpression/knockdown cells |
| PPARγ | Osteoarthritis, cholesterol metabolism | PPARγ knockout chondrocytes |
Cancer and lipid metabolism reprogramming
In many cancers, upregulated fatty acid synthesis supports rapid proliferation. FASN, which harbors acetyltransferase activity, is overexpressed in ovarian cancer, where USP43 stabilizes FASN and activates SLC7A11 to suppress ferroptosis. In hepatocellular carcinoma, Riplet promotes lipid metabolism changes associated with CD8 T cell exhaustion and anti-PD-1 resistance. Targeting acetyltransferase activity may therefore enhance immunotherapy efficacy.
Immune cell function and tumor microenvironment
Lipid signaling enforces functional specialization of regulatory T cells in tumors, with mTOR and lipid metabolism playing key roles. Acetyltransferase-dependent lipid synthesis influences Treg suppressive function and may contribute to immune evasion. Modulating GO:0004313 could alter T cell fate and anti-tumor immunity.
Metabolic and inflammatory diseases
Alterations in lipid metabolism are observed in COVID-19, where the fatty acid lipid metabolism nexus affects disease severity. In osteoarthritis, cholesterol metabolism-related genes, potentially including acetyltransferase components, are dysregulated. These findings suggest that GO:0004313 may be relevant to inflammatory and degenerative conditions.
From [acyl-carrier-protein] S-acetyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of acetyltransferase activity reduce fatty acid synthesis? | CRISPR knockout of FASN or MCAT in cell lines |
| How does a point mutation in the catalytic domain affect enzyme kinetics? | CRISPR point mutation knock-in of catalytic residues |
| Can tagging the enzyme reveal its localization? | Knock-in of fluorescent tag (e.g., GFP) |
| Does overexpression drive lipid accumulation? | Overexpression of FASN or ACACA |
| Which genes regulate acetyl-ACP levels? | CRISPR library screening with lipid readouts |
| How does acetyltransferase activity affect immune cell function? | Knockout in primary T cells or mouse models |
How to Study the [acyl-carrier-protein] S-acetyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screening | Gene essentiality and lipid phenotypes | Identify regulators of acetyltransferase activity |
| Lipidomics | Lipid species and acetyl-ACP levels | Quantify fatty acid synthesis flux |
| RNA-seq | Transcriptional changes | Assess lipogenic gene expression |
| Proteomics | Protein abundance and modifications | Evaluate FASN stability |
| Metabolomics | Metabolite pools including acetyl-CoA | Measure pathway flux |
| Enzyme activity assay | Catalytic rate of acetyl transfer | In vitro kinetics |
| Fluorescence imaging | Subcellular localization | Track tagged ACP |
| CRISPR library screening | Pooled gene function | Discover novel regulators |
CRISPR screening and functional genomics
Genome-wide CRISPR knockout screens can identify genes that regulate acetyltransferase activity and lipid metabolism. For example, screens in cancer cells have uncovered modifiers of FASN-dependent ferroptosis and lipid reprogramming. These screens are powerful for discovering novel regulators of GO:0004313.
Lipidomics and metabolomics
Mass spectrometry-based lipidomics quantifies acetyl-ACP and downstream fatty acids, providing direct readouts of acetyltransferase activity. Metabolomics can trace 13C-labeled acetyl-CoA into lipid pools to measure flux.
Transcriptomics and proteomics
RNA-seq reveals expression changes in lipogenic genes, while proteomics assesses FASN stability and post-translational modifications. These methods help link genotype to phenotype in CRISPR models.
Imaging and reporter assays
Fluorescent reporters or tagged ACP can visualize acetyl-ACP localization and dynamics in live cells. Enzyme activity assays using radiolabeled acetyl-CoA measure catalytic rates in vitro.
How CRISPR Can Be Used to Study GO:0004313 [acyl-carrier-protein] S-acetyltransferase activity
Knockout
CRISPR knockout of FASN or other acetyltransferase genes abolishes GO:0004313 activity, leading to reduced fatty acid synthesis and growth defects in cancer cells. Knockout models are essential to establish causality between the enzyme and lipid-dependent phenotypes.
Point Mutation
Introducing point mutations in the catalytic domain of FASN or MCAT can dissect the contribution of acetyltransferase activity versus other enzymatic functions. Such models help distinguish substrate binding from catalysis.
Knock-in
Knock-in of epitope tags or fluorescent proteins allows tracking of acetyltransferase enzymes in live cells and tissues. Knock-in of disease-associated mutations can model human disorders linked to lipid metabolism.
Overexpression
Overexpression of FASN or ACACA increases acetyl-ACP production and lipid accumulation, mimicking the lipogenic phenotype of cancer cells. Overexpression models are useful for testing inhibitors of GO:0004313.
How EDITGENE Supports [acyl-carrier-protein] S-acetyltransferase activity Research
Researchers studying [acyl-carrier-protein] S-acetyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in lipid metabolism, immune regulation, or disease progression. EDITGENE provides comprehensive CRISPR services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for [acyl-carrier-protein] S-acetyltransferase activity research.
Frequently Asked Questions About [acyl-carrier-protein] S-acetyltransferase activity
What is GO:0004313?
GO:0004313 is the Gene Ontology term for [acyl-carrier-protein] S-acetyltransferase activity, which catalyzes the transfer of an acetyl group from acetyl-CoA to an acyl-carrier protein, forming acetyl-ACP and CoA.
What genes are involved in [acyl-carrier-protein] S-acetyltransferase activity?
Key genes include FASN, MCAT, ACACA, and ACACB, which encode enzymes that directly or indirectly support acetyl transfer to ACP.
What diseases are associated with [acyl-carrier-protein] S-acetyltransferase activity?
Dysregulation is linked to cancer (e.g., ovarian, hepatocellular), immune exhaustion, COVID-19, and osteoarthritis.
How is [acyl-carrier-protein] S-acetyltransferase activity regulated?
It is regulated transcriptionally by SREBP1 and PPARγ, post-translationally by ubiquitination (e.g., USP43), and via nutrient signaling (mTOR, AMPK).
What is the reaction catalyzed by GO:0004313?
The reaction is: acetyl-CoA + [acyl-carrier protein] = CoA + acetyl-[acyl-carrier protein].
Why is [acyl-carrier-protein] S-acetyltransferase activity important in cancer?
It supplies acetyl-ACP for fatty acid synthesis, supporting membrane production and survival signaling in cancer cells.
How can CRISPR be used to study GO:0004313?
CRISPR knockout, point mutation, knock-in, and overexpression models allow functional dissection of the enzyme in lipid metabolism and disease.
What methods measure [acyl-carrier-protein] S-acetyltransferase activity?
Enzyme activity assays, lipidomics, metabolomics, and CRISPR screening are commonly used.
Is [acyl-carrier-protein] S-acetyltransferase activity involved in immune regulation?
Yes, it influences T cell exhaustion and regulatory T cell function in tumors.
What cell models are available for studying GO:0004313?
Knockout, point mutation, knock-in, and overexpression cell lines can be generated for genes like FASN and MCAT.
Conclusion
GO:0004313, [acyl-carrier-protein] S-acetyltransferase activity, is a fundamental enzymatic function that primes fatty acid biosynthesis and impacts cancer, immunity, and metabolic diseases. Understanding its regulation and role in disease requires robust experimental models. CRISPR-based knockout, point mutation, knock-in, and overexpression approaches, combined with lipidomics and screening, provide powerful tools to dissect this activity. EDITGENE offers end-to-end services to support such research and accelerate therapeutic discovery.
References
- 1. Liang J et al.. 2025. Riplet promotes lipid metabolism changes associated with CD8 T cell exhaustion and anti-PD-1 resistance in hepatocellular carcinoma.. Sci Immunol 10(108):eado3485 PMID: 40577442
- 2. Lim SA et al.. 2021. Lipid signalling enforces functional specialization of T(reg) cells in tumours.. Nature 591(7849):306-311 PMID: 33627871
- 3. Wang L et al.. 2024. MK8722 initiates early-stage autophagy while inhibiting late-stage autophagy via FASN-dependent reprogramming of lipid metabolism.. Theranostics 14(1):75-95 PMID: 38164137
- 4. Chen X et al.. 2023. High-intensity interval training induces lactylation of fatty acid synthase to inhibit lipid synthesis.. BMC Biol 21(1):196 PMID: 37726733
- 5. Zhao T et al.. 2025. YY1-induced USP43 drives ferroptosis suppression by FASN stabilization and subsequent activation of SLC7A11 in ovarian cancer.. Cell Death Dis 16(1):589 PMID: 40890129
- 6. Tanner JE et al.. 2021. The Fatty Acid Lipid Metabolism Nexus in COVID-19.. Viruses 13(1) PMID: 33440724
- 7. Huang C et al.. 2015. Lipid metabolism, apoptosis and cancer therapy.. Int J Mol Sci 16(1):924-49 PMID: 25561239
- 8. Lao C et al.. 2025. Screening biomarkers related to cholesterol metabolism in osteoarthritis based on transcriptomics.. Sci Rep 15(1):21218 PMID: 40593053
