GO:0016746 acyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016746 acyltransferase activity is a molecular function defined as catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor) [QuickGO].
• Acyltransferases include ghrelin O-acyltransferase (GOAT), monoacylglycerol acyltransferase (MGAT), and ZDHHC-family S-palmitoyltransferases, which regulate energy metabolism, lipid synthesis, and oncogenic signaling [3,5,7].
• Acyltransferase activity is central to inflammation, as NLRP3 phase separation and inflammasome activation depend on acylation-related signaling events.
• Exercise and metabolic stress reprogram acyltransferase-dependent pathways, including FOXO1-KLF10 lipolysis and cardiac metabolic remodeling [2,8].
• Dysregulated acyltransferase activity contributes to cancer, metabolic disease, and cardiovascular pathology, making these enzymes attractive therapeutic targets [3,7,8].
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of acyltransferase genes in disease and metabolism [1,2,7].
Description
Acyltransferase activity (GO:0016746) is a fundamental molecular function in which an acyl group is transferred from a donor molecule to an acceptor molecule [QuickGO]. This enzymatic activity underlies diverse biological processes, including lipid biosynthesis, protein lipidation, and metabolic signal transduction. Researchers study acyltransferases because they control the chemical modification of proteins and lipids that govern energy balance, inflammation, and cell survival [3,5,7]. The importance of acyltransferase activity extends from basic biochemistry to human disease. Ghrelin O-acyltransferase (GOAT) activates ghrelin, a hormone that regulates appetite and energy metabolism, linking acylation directly to metabolic control. Monoacylglycerol acyltransferase (MGAT) catalyzes a key step in triacylglycerol synthesis, and its activity is developmentally regulated in the liver. S-palmitoylation, mediated by ZDHHC acyltransferases, promotes STAT3 activation and is amplified in cancer, demonstrating how acyltransferase activity can drive oncogenesis. Recent work shows that acyltransferase-dependent processes are responsive to physiological cues. Exercise induces anti-obesity effects through a FOXO1-KLF10 reinforcing loop that promotes adipose lipolysis, and the muscle-specific MEF2Dα2 isoform supports ketolysis and running capacity. Cardiac metabolic reprogramming in response to exercise or pathological stress is governed by transcription factor Yin-Yang 1. These findings position acyltransferase activity as a nexus between metabolism, gene regulation, and disease, and they motivate the use of CRISPR-based models to dissect causal mechanisms.
acyltransferase activity At A Glance
| GO ID | GO:0016746 |
|---|---|
| GO term | acyltransferase activity |
| Ontology | molecular_function |
| Synonym | transferase activity, transferring acyl groups |
| Definition | Catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor). |
| Major function | Transfer of acyl groups to lipids, proteins, and small molecules, controlling metabolism and signaling. |
| Example enzymes | GOAT, MGAT, ZDHHC19, and other acyltransferases [3,5,7]. |
| Disease relevance | Cancer, metabolic disorders, cardiovascular disease, and inflammation [1,3,7,8]. |
| Research methods | CRISPR KO/point mutation/knock-in/overexpression, lipidomics, proteomics, and metabolic assays [1,2,7]. |
What Is GO:0016746?
According to the Gene Ontology, GO:0016746 acyltransferase activity is defined as catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor) [QuickGO]. In practical terms, an acyltransferase enzyme takes a fatty-acid-derived acyl group from a donor molecule, such as acyl-CoA, and attaches it to a target acceptor, which may be a lipid, a protein, or another small molecule. This activity is classified as a molecular_function and is synonymous with transferase activity, transferring acyl groups [QuickGO]. The reaction is central to building and modifying lipids and to attaching acyl groups to proteins, thereby changing their localization, stability, or signaling capacity [3,5,7].
Why Is acyltransferase activity Important in Cell Biology?
Acyltransferase activity is important because it controls the covalent attachment of acyl groups to diverse biomolecules, thereby regulating energy metabolism, protein trafficking, inflammation, and cell growth [3,5,7]. Dysregulation of acyltransferases is linked to cancer, metabolic disease, and cardiovascular pathology, and these enzymes are increasingly recognized as druggable nodes in disease pathways [1,7,8]. Understanding acyltransferase activity at the molecular level therefore provides mechanistic insight into both normal physiology and disease, and it supports the development of targeted therapies.
• Acyltransferase activity is required for ghrelin activation by GOAT, which regulates appetite and energy metabolism.
• MGAT catalyzes a committed step in triacylglycerol synthesis, influencing hepatic lipid storage.
• ZDHHC19-mediated S-palmitoylation promotes STAT3 activation and is amplified in cancer.
• Acyltransferase-dependent signaling participates in NLRP3 inflammasome activation and inflammation.
• Exercise-induced anti-obesity effects involve FOXO1-KLF10 regulation of adipose lipolysis.
• Muscle ketolysis and running capacity are supported by the MEF2Dα2 isoform, linking acylation to exercise performance.
• Cardiac metabolic reprogramming under exercise or pathological stress is governed by Yin-Yang 1.
• Acyltransferase activity is a potential therapeutic target in cancer and metabolic disease [3,7].
• CRISPR models enable causal testing of acyltransferase gene function in vivo and in vitro [1,2,7].
• Acyltransferases are tractable for high-throughput screening and bioinformatics analysis of metabolic networks [3,5].
Molecular Mechanism of acyltransferase activity
Substrate recognition and donor selection
In simple terms: The enzyme first grabs the acyl group from a donor molecule.
Acyltransferases recognize specific donor molecules, most commonly acyl-CoA thioesters, and position the acyl group for transfer to an acceptor [3,5]. For example, GOAT transfers an octanoyl group from octanoyl-CoA to ghrelin, a modification required for ghrelin activity. MGAT uses acyl-CoA donors to acylate monoacylglycerol, forming diacylglycerol in the triacylglycerol synthesis pathway. The specificity of donor selection determines which acyl chains are incorporated into lipids or proteins.
Catalytic transfer to acceptor
In simple terms: The acyl group is handed off to the target molecule.
Once the donor and acceptor are bound, the enzyme catalyzes the transfer of the acyl group to a nucleophilic acceptor, such as a hydroxyl or thiol group [5,7]. In protein S-palmitoylation, ZDHHC enzymes transfer palmitate to cysteine residues of substrate proteins like STAT3, thereby promoting STAT3 activation. In lipid synthesis, MGAT transfers acyl groups to monoacylglycerol to produce diacylglycerol. This step is often rate-limiting and is tightly regulated by substrate availability and enzyme localization.
Cofactors and membrane association
In simple terms: Many acyltransferases need membranes and cofactors to work.
Many acyltransferases are integral membrane proteins that require a lipid bilayer environment for activity [5,7]. MGAT is associated with the endoplasmic reticulum membrane, where it accesses lipid substrates. ZDHHC enzymes are polytopic membrane proteins that use a conserved DHHC cysteine-rich domain to coordinate zinc and catalyze palmitoyl transfer. These structural features ensure that acyl transfer occurs at the correct subcellular site.
Regulation by metabolic and inflammatory signals
In simple terms: Cellular signals can turn acyltransferase activity up or down.
Acyltransferase activity is regulated by metabolic state and inflammatory cues. NLRP3 phase separation initiates inflammasome activation, a process that depends on acylation-related signaling events. Exercise induces a FOXO1-KLF10 reinforcing loop that promotes adipose lipolysis, implicating acyltransferase-dependent lipid remodeling. Cardiac metabolic reprogramming in response to exercise or pathological stress is controlled by Yin-Yang 1, which may influence acyltransferase gene expression. These examples show that acyltransferase activity is integrated into broader physiological networks.
Downstream consequences for signaling and metabolism
In simple terms: The acyl group changes how the target molecule behaves.
Acylation alters the function of target molecules. Ghrelin acylation by GOAT is required for ghrelin to stimulate appetite and regulate energy balance. S-palmitoylation of STAT3 by ZDHHC19 promotes STAT3 activation and supports cancer cell proliferation. In muscle, the MEF2Dα2 isoform promotes ketolysis and running capacity, linking acyltransferase-related metabolism to exercise performance. Thus, acyltransferase activity has broad downstream effects on physiology and disease.
Key Genes Involved in GO:0016746 acyltransferase activity
The following genes encode enzymes or regulators directly implicated in acyltransferase activity and its biological roles, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| GOAT | Ghrelin O-acyltransferase; acylates ghrelin | Energy metabolism and appetite regulation |
| MGAT | Monoacylglycerol acyltransferase; synthesizes diacylglycerol | Hepatic lipid metabolism and development |
| ZDHHC19 | S-palmitoyltransferase; palmitoylates STAT3 | Cancer signaling and STAT3 activation |
| NLRP3 | Inflammasome sensor; phase separation upon signaling | Inflammation and innate immunity |
| FOXO1 | Transcription factor; promotes lipolysis | Exercise-induced anti-obesity effects |
| KLF10 | Transcription factor; part of FOXO1-KLF10 loop | Adipose lipolysis and metabolic regulation |
| MEF2D | Muscle-specific isoform MEF2Dα2; promotes ketolysis | Exercise capacity and muscle metabolism |
| YY1 | Transcription factor; governs cardiac metabolic reprogramming | Cardiac response to exercise and stress |
| STAT3 | Transcription factor; activated by S-palmitoylation | Cancer and inflammation |
| Ghrelin | Hormone; requires acylation for activity | Appetite and energy balance |
| Monoacylglycerol | Substrate for MGAT | Lipid synthesis |
| Acyl-CoA | Donor of acyl groups | Central metabolite for acyltransferases [3,5] |
| Palmitoyl-CoA | Donor for S-palmitoylation | Protein lipidation |
| DHHC domain | Catalytic domain of ZDHHC enzymes | Palmitoyl transfer |
| Inflammasome | Multiprotein complex; activated by NLRP3 | Inflammation |
| Adipose tissue | Site of lipolysis regulated by FOXO1-KLF10 | Metabolic disease |
| Cardiomyocyte | Cell type with metabolic reprogramming by YY1 | Cardiovascular disease |
How Is acyltransferase activity Regulated?
Acyltransferase activity is regulated at multiple levels. Transcriptional control by FOXO1 and KLF10 modulates adipose lipolysis in response to exercise, while Yin-Yang 1 governs cardiac metabolic reprogramming under exercise or pathological stress. Inflammatory signaling triggers NLRP3 phase separation, which initiates inflammasome activation and may influence acylation-dependent processes. Substrate availability, such as acyl-CoA levels, and membrane localization further regulate enzyme activity [3,5,7]. These layers of regulation ensure that acyltransferase activity is matched to cellular metabolic demands.
acyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ZDHHC19 | Cancer; STAT3 activation | Knockout and overexpression in cancer cell lines |
| GOAT | Metabolic disorders; energy imbalance | Knockout mouse models and ghrelin acylation assays |
| MGAT | Hepatic lipid metabolism; steatosis | Liver-specific knockout and lipidomics |
| NLRP3 | Inflammatory diseases; inflammasome activation | Point-mutation and knockout macrophages |
| FOXO1/KLF10 | Obesity; adipose lipolysis | Adipose-specific knockout and exercise models |
Acyltransferase activity in cancer
Cancer-amplified ZDHHC19 promotes STAT3 activation through S-palmitoylation, linking acyltransferase activity to oncogenic signaling. This suggests that inhibitors of ZDHHC19 or related acyltransferases could disrupt STAT3-driven tumors. The dependence of cancer cells on lipid modification pathways makes acyltransferases attractive therapeutic targets.
Acyltransferase activity in metabolic and cardiovascular disease
GOAT-mediated ghrelin acylation regulates energy metabolism, and dysregulation of this axis contributes to obesity and metabolic disorders. Exercise-induced anti-obesity effects involve FOXO1-KLF10-dependent lipolysis, highlighting acyltransferase-related pathways in metabolic health. Cardiac metabolic reprogramming by Yin-Yang 1 in response to stress suggests that acyltransferase activity participates in cardiovascular pathology.
Acyltransferase activity in inflammation
NLRP3 phase separation initiates inflammasome activation, a central process in inflammatory diseases. Acylation events may modulate NLRP3 signaling, and targeting acyltransferases could provide anti-inflammatory strategies. This connection broadens the disease relevance of acyltransferase activity beyond metabolism and cancer.
From acyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of acyltransferase gene X reduce tumor growth? | CRISPR knockout in cancer cell lines and xenografts |
| Does a specific catalytic residue mediate acyl transfer? | Point-mutation knock-in of catalytic cysteine |
| Does acyltransferase activity regulate energy metabolism? | Knockout mouse models with metabolic phenotyping |
| Does acylation of a target protein affect its function? | Tagged knock-in for affinity purification and proteomics |
| Does overexpression of an acyltransferase drive inflammation? | Overexpression in macrophages and inflammasome assays |
| Does exercise-induced lipolysis require acyltransferase activity? | Adipose-specific knockout with exercise intervention |
How to Study the acyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics | Acylated lipid species | Quantifying triacylglycerol changes |
| Acyl-CoA profiling | Donor substrate levels | Metabolic flux analysis |
| S-palmitoylation proteomics | Protein acylation sites | Identifying ZDHHC substrates |
| Metabolic cages | Energy expenditure and food intake | Metabolic phenotyping |
| Exercise performance tests | Running capacity and ketolysis | Muscle metabolism studies |
| Fluorescence microscopy | Protein condensation and localization | Inflammasome activation |
| CRISPR screening | Gene essentiality and pathway discovery | Identifying acyltransferase dependencies |
Lipidomics and acyl-CoA profiling
Mass spectrometry-based lipidomics measures the abundance of acylated lipids and acyl-CoA species, providing a readout of acyltransferase activity. This approach can quantify changes in triacylglycerol and diacylglycerol levels upon genetic perturbation.
Proteomics for protein acylation
Click-chemistry or acyl-biotin exchange proteomics identifies proteins modified by S-palmitoylation, revealing substrates of ZDHHC enzymes. This method can map acylation sites and quantify changes in response to knockout or overexpression.
Metabolic and exercise phenotyping
Metabolic cages, running wheels, and exercise tests assess energy balance and performance in models with altered acyltransferase activity [2,6]. These assays link molecular function to whole-body physiology [2,6].
Imaging and phase separation assays
Fluorescence microscopy and phase separation assays visualize NLRP3 condensation and inflammasome activation, which are influenced by acylation-related signaling. These methods provide spatial and dynamic information about acyltransferase-dependent processes.
How CRISPR Can Be Used to Study GO:0016746 acyltransferase activity
Knockout
CRISPR knockout of acyltransferase genes such as ZDHHC19 or GOAT eliminates enzyme activity, enabling assessment of loss-of-function phenotypes in cancer and metabolism [3,7]. Knockout models can reveal whether a specific acyltransferase is required for STAT3 activation or ghrelin signaling [3,7].
Point Mutation
Point mutation of catalytic residues, such as the DHHC cysteine in ZDHHC enzymes, abolishes acyltransferase activity while preserving protein expression. This approach distinguishes catalytic function from scaffolding roles and can be used to validate substrate specificity.
Knock-in
Knock-in of tagged or reporter alleles allows tracking of acyltransferase expression and localization in vivo. Tagged knock-in can facilitate affinity purification of acylated proteins and interaction partners.
Overexpression
Overexpression of acyltransferases such as ZDHHC19 or GOAT can drive pathway activation and model disease states, including cancer and metabolic imbalance [3,7]. Overexpression studies complement knockout approaches to establish sufficiency [3,7].
How EDITGENE Supports acyltransferase activity Research
Researchers studying acyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in a specific metabolic, inflammatory, or oncogenic process. CRISPR-based models provide the necessary tools to test causality by precisely manipulating gene function in relevant cell types and organisms.
Contact EDITGENE today to design your custom CRISPR model for acyltransferase activity research.
Frequently Asked Questions About acyltransferase activity
What is acyltransferase activity?
Acyltransferase activity (GO:0016746) is a molecular function defined as catalysis of the transfer of an acyl group from one compound (donor) to another (acceptor) [QuickGO].
What genes are involved in acyltransferase activity?
Key genes include GOAT, MGAT, and ZDHHC19, which encode enzymes that transfer acyl groups to ghrelin, lipids, and proteins, respectively [3,5,7].
How is acyltransferase activity regulated?
It is regulated by transcription factors such as FOXO1, KLF10, and Yin-Yang 1, as well as by substrate availability and inflammatory signals [1,2,8].
What diseases are linked to acyltransferase activity?
Dysregulated acyltransferase activity is linked to cancer, metabolic disorders, cardiovascular disease, and inflammation [1,3,7,8].
What is the role of GOAT in energy metabolism?
GOAT acylates ghrelin, a modification required for ghrelin to regulate appetite and energy balance.
How does ZDHHC19 contribute to cancer?
ZDHHC19-mediated S-palmitoylation promotes STAT3 activation and is amplified in cancer, supporting oncogenic signaling.
What methods are used to study acyltransferase activity?
Common methods include lipidomics, S-palmitoylation proteomics, metabolic phenotyping, and CRISPR-based genetic models [1,2,5,7].
Can CRISPR knockout be used to study acyltransferase genes?
Yes, CRISPR knockout of acyltransferase genes such as ZDHHC19 and GOAT enables loss-of-function studies in disease models [3,7].
What is the connection between acyltransferase activity and exercise?
Exercise induces FOXO1-KLF10-dependent lipolysis and muscle MEF2Dα2-mediated ketolysis, linking acyltransferase-related metabolism to exercise capacity [2,6].
How does NLRP3 relate to acyltransferase activity?
NLRP3 phase separation initiates inflammasome activation, a process influenced by acylation-related signaling events.
Conclusion
Acyltransferase activity (GO:0016746) is a central molecular function that governs lipid synthesis, protein lipidation, and metabolic signaling [3,5,7]. Its dysregulation contributes to cancer, metabolic disease, cardiovascular pathology, and inflammation, making it a high-value target for mechanistic and therapeutic research [1,3,7,8]. CRISPR-based knockout, point-mutation, knock-in, and overexpression models provide powerful tools to dissect the causal roles of acyltransferases in health and disease. EDITGENE offers comprehensive services to accelerate discovery in this field.
References
- 1. Zou G et al.. 2025. Signal-induced NLRP3 phase separation initiates inflammasome activation.. Cell Res 35(6):437-452 PMID: 40164768
- 2. Zhu JY et al.. 2025. Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis.. Nat Commun 16(1):3111 PMID: 40169574
- 3. Li Z et al.. 2016. Ghrelin O-acyltransferase (GOAT) and energy metabolism.. Sci China Life Sci 59(3):281-91 PMID: 26732975
- 5. Coleman RA et al.. 1984. Hepatic monoacylglycerol acyltransferase. Characterization of an activity associated with the suckling period in rats.. J Biol Chem 259(14):8934-8 PMID: 6746631
- 6. Kumar S et al.. 2025. The muscle specific MEF2Dα2 isoform promotes muscle ketolysis and running capacity in mice.. EMBO Rep 26(21):5216-5238 PMID: 40958050
- 7. Niu J et al.. 2019. Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation.. Nature 573(7772):139-143 PMID: 31462771
- 8. Zhang M et al.. 2025. Transcription factor Yin-Yang 1 governs cardiac metabolic reprogramming in response to exercise or pathological stress.. Am J Physiol Heart Circ Physiol 329(4):H899-H906 PMID: 40803696
