Histone deacetylase 11 is a fatty-acid deacylase
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Abstract
ABSTRACT Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity. Here we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8–18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate. Additionally, N-linked lipoic acid and biotin are removed by the enzyme, although with lower efficacy. Catalytic efficiencies toward dodecanoylated and myristoylated peptides exceed 70,000 M −1 s −1 making HDAC11 the most proficient fatty acid deacylase of the HDAC family. Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic and stearic acids with inhibition constants of 6.5 µM, 0.9 µM, and 1.6 µM, respectively. At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty acid metabolites. Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
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HDAC11 shows strong activity toward long-chain acyl groups and plays a role in lipid metabolism.
“HDAC11 shows strong activity toward long-chain acyl groups and plays a role in lipid metabolism (Moreno-Yruela et al., 2018; Kutil et al., 2018).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Kutil et al., 2018
The Results and Discussion report efficient removal of fatty-acyl groups, especially decanoyl and dodecanoyl groups, but much lower efficiency for 16–18-carbon chains. The same section suggests that HDAC11 could sense fatty-acid metabolism; it does not establish that HDAC11 plays a role in lipid metabolism. (LLM, conf=0.87)
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- Authors
- Kutil, Z., Novakova, Z., Meleshin, M., Mikesova, J., Schutkowski, M., & Barinka, C.
- Affiliations
- Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic
- Martin Luther University Halle-Wittenberg (DE)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-01-16
- Volume
- 13
- Issue
- 3
- Pages
- 685-693
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- OpenAlex
- W2782749817
- Cited by
- 174
- References
- 36
- Citations by year
- 2026: 22 · 2025: 21 · 2024: 23 · 2023: 25 · 2022: 14 · 2021: 17 · 2020: 19 · 2019: 20 · 2018: 13
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- ACS Chemical Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- European Regional Development Fund
- Akademie Ved Cesk? Republiky (86652036)
- Grantov? Agentura Cesk? Republiky (15-19640S)
- BIOCEV (CZ.1.05/1.1.00/02.0109)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- HDAC11, myristoylation, palmitoylation, alpha-lipoic acid, biotin, fatty acid inhibition, fatty acid metabolites, coenzyme A, histone deacetylase inhibitors, enzyme kinetics
- MeSH terms
- Acetyl-CoA Hydrolase, Enzyme Inhibitors, Fatty Acids, Histone Deacetylases, Lysine, Peptides, Substrate Specificity, Drug Design
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