Advance in Metabolite-mediated Non-enzymatic Post-translational Modifications

doi:10.13523/j.cb.2304037

China Biotechnology

2023, Vol. 43

Issue (10): 43-51 DOI: 10.13523/j.cb.2304037

Advance in Metabolite-mediated Non-enzymatic Post-translational Modifications

DONG Yuan-yuan,BAO Qiu-yu,WANG De-xiang,WEN Hong-tao,YANG Xing-chao,WAN Ning^**(

),YE Hui^**(

)

Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Abstract

Endogenous small molecules play vital roles in the cell lifespan, such as supplying the energy and substrates for biological processes and mediating cellular communication. Previous studies have shown that some endogenous reactive molecules can non-enzymatically modify proteins via spontaneous chemical reactions, thereby regulating protein structure and functions and participating in various cellular processes. Recently, the rapid development of proteomics technology for capturing non-enzymatically modified target proteins contributes to elucidating the function of the modified target protein. This review focuses on reversible and irreversible non-enzymatic covalent modifications (NECMs) produced by active metabolites, respectively, and introduces the formation mechanism of NECMs and the application of proteomics in the discovery of new post-translational modifications (PTMs) and the elucidation of metabolites-regulated protein functions.

Key words： Reactive metabolite Non-enzymatic covalent modifications Proteomics

Received: 18 April 2023 Published: 02 November 2023

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	DONG Yuan-yuan
	BAO Qiu-yu
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	WEN Hong-tao
	YANG Xing-chao
	WAN Ning
	YE Hui

Cite this article:

DONG Yuan-yuan, BAO Qiu-yu, WANG De-xiang, WEN Hong-tao, YANG Xing-chao, WAN Ning, YE Hui. Advance in Metabolite-mediated Non-enzymatic Post-translational Modifications. China Biotechnology, 2023, 43(10): 43-51.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2304037 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I10/43

Fig.1 Structures of the common LDEs and carbonylation reactions (a) Structures of the common LDEs (b) Reaction pathways of ACR with nucleophilic amino acids (cysteine, lysine, histidine)

Fig.2 Workflow of ABPP analysis The ABPP technology is based on activity-based probes (ABPs) which mimic the chemical structure of reactive metabolites to discover the modified target proteins

Fig.3 The formation of glycation on nucleophilic amino acids (a) The reactions between MGO and nucleophilic amino acids (arginine and lysine) (b) The formation of mercaptomethylimidazole modification

Fig.4 The formation of succination on cysteine

Fig.5 Non-enzymatic acylation mediated by acyl-CoA

Fig.6 Non-enzymatic lactoylation mediated by LGSH (a) The formation of LGSH (b) The formation of non-enzymatic acylation

Fig.7 Non-enzymatic phosphorylation (a) The formation of polyphosphorylation (b) The formation of pyrophosphorylation

Table 1 The non-enzymatic covalent modifications induced by active metabolites


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