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A chemical catalyst enabling histone acylation with endogenous acyl-CoA
Misuzu Habazaki1, Shinsuke Mizumoto1, Hidetoshi Kajino1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Nature Communications
|September 22, 2023
Summary
Researchers developed a small-molecule catalyst, mBnA, that mimics histone acetyltransferase activity. This novel catalyst activates endogenous cellular molecules, enabling histone modifications in living cells for disease research.
Area of Science:
- Biochemistry
- Chemical Biology
- Molecular Biology
Background:
- Enzyme abnormalities are linked to various diseases.
- Small-molecule enzyme surrogates are valuable tools for studying and treating diseases.
- Developing catalysts for low-concentration cellular metabolites remains a challenge.
Purpose of the Study:
- To develop a small-molecule catalyst that can surrogate for malfunctional endogenous enzymes.
- To activate endogenous acyl-CoAs and promote histone lysine acylations in living cells.
Main Methods:
- Designed a small-molecule catalyst, mBnA, with a hydroxamic acid moiety.
- Utilized a thiol-thioester exchange process for catalyst activation.
- Demonstrated mBnA's ability to activate endogenous acyl-CoAs in living cells.
Main Results:
- mBnA successfully mimicked histone acetyltransferase activity.
- The catalyst activated low-concentration endogenous acyl-CoAs.
- Histone lysine acylations were promoted in living cells without exogenous acyl donors.
Conclusions:
- mBnA serves as an effective enzyme surrogate for histone acetyltransferase.
- This approach enables the study and manipulation of cellular chemistry in disease contexts.
- Enzyme surrogates utilizing cellular metabolites offer a unique tool for biological research.
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