CHEMICAL SCIENCE

Semi-synthetic biosensors reveal coenzyme A metabolic balance


Xue Lin’s research group, a special professor of the Department of Life Science and Medicine of the University of Science and Technology of China, and Kai Johnsson, professor at the Max Planck Institute for Medical Research in Germany, have constructed and used semi-synthetic biosensors to reveal metabolic balance in CoA (CoA) cells. On October 31, the relevant research results were published online in Nature Chemical Biology.

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CoA semi-synthetic biosensors and reinterpretation of CoA metabolic equilibrium Courtesy of respondents

CoA is synthesized by vitamin B5 in the body and is one of the most important metabolites (coenzymes) in the human body, which is involved in many metabolic pathways in the body, such as the tricarboxylic acid cycle, amino acid metabolism, protein post-translational modification, and gene expression regulation. “Studies have proved that the occurrence and development of metabolic diseases such as neurodegenerative diseases, obesity and tumors are closely related to the metabolic imbalance of CoA.” Xue Lin introduced.

However, since the discovery of intracellular CoA in 1946, no effective method has been found to accurately detect its concentration and distribution in living cells, resulting in unclear how cells regulate the balance and metabolic process of CoA, and the molecular mechanism of related diseases is poorly understood.

In this work, the researchers used protein labeling to construct a semi-synthetic biosensor for CoA. “This sensor is a complex of self-labeled proteins, fluorescent proteins, and CoA receptor proteins. It has fluorescence, and the fluorescence color changes after binding to CoA, and then the quantitative detection of CoA is realized by detecting the change of fluorescence color. Xue Lin explained.

The researchers further used the sensor to achieve the in situ analysis of CoA in the cytoplasm and mitochondria of living cells for the first time, revealing the equilibrium and metabolic regulation mechanism of CoA in subcells. Using fluorescence lifetime imaging, researchers have also achieved the first accurate determination of free CoA concentrations in the cytoplasm and mitochondria of different cell lines.

Xue Lin said, “From this, we provide highly effective molecular tools for the development of inhibitors or drugs for neurological and metabolic diseases related to CoA metabolism, which will help realize the treatment of tumors and other diseases.” In addition, I hope that CoA sensors can be used by more biologists to reveal more CoA-related life science questions. ”

“CoA has a central role in energy and fat metabolism, and how to detect its fluctuations within cells has long puzzled biologists, and Dr. Xue and his collaborators first reported CoA-specific biosensors that directly address these challenges and provide elegant solutions to these problems,” the reviewers said. (Source: Wang Min, China Science Daily)

Related Paper Information: https://doi.org/10.1038/s41589-022-01172-7



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