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The Chinese team has shown its sword again and published a blockbuster scientific progress in the journal "Cell"!
Just last night, on April 22, 2024, Cell launched a paper led by Professor Jiang Changtao of Peking University and jointly communicated by Academician Qiao Jie, Professor Pang Yanli, Professor Jia Yanxing of Peking University, and Professor Zheng Minghua of Wenzhou Medical University.
Like the Cheng Gong I introduced a few days ago, Changtao is also a good friend of mine, and they have made breakthroughs in the past few days, and they have collected all the big CNS articles, which is really happy!
The paper led by Chang Tao shows their newly discovered type of bile acid modification - 3-acylation, in which it locks the "monomorphic bacteroides" in the intestine to produce a new 3-succinylcholic acid, and explains how this bile acid is distributed in people with liver problems, and which enzyme it is produced by, how it promotes the growth of AKK bacteria, and ultimately how to improve the intestinal barrier and liver problems.
It's a beautiful study! Of course, there's a lot of work behind it.
Step 1: Bacterial bile acid mining system and 3-acylylated bile acid structure
In the first step, they first take the microorganisms in human poop and add bile acids with molecular probes, and the microorganisms will "eat", that is, metabolize these bile acids, and then use substances that can identify probes to enrich various bile acids produced by microorganisms after "gnawing", and then do mass spectrometry to see what is new in it.
They were fortunate to discover a new range of bile acids that included formylation, acetylation, succinylation, etc. (chemical terms I almost forget), and also locked in the highest content of 3-succinylcholic acid.
Step 2: The intestinal strain library screens for 3-sucCA-producing bacteria
The second step is to find out who produces 3-succinylcholic acid. As shown in the figure above, they isolated and cultured hundreds of microorganisms, tried them one by one, and finally found the "Bacteroides monoforma", the little guy with the highest yield. I don't know which postdoc or student did the work, and I feel quite tired!
Step 3: Activity-based protein purification and identification to discover 3-sucCA synthetase
Of course, the third step is just as tiring! They have to find out which enzyme synthesizes 3-succinylcholic acid. At first, 16 genes that look like acyltransferases were overexpressed in E. coli, and it was found that none of them were there. Then they made a trick and fished out 118 candidate proteins in Bacteroides monoforma and put them all into E. coli to express them.
16+118=134!With so many protein expressions and functional verifications, as a "Tsinghua scum" who has done these experiments, I think about it...... But Changtao and they worked hard to make it, and had the last laugh and locked the enzyme.
Step 4: Mouse experiments and clinical cohorts to elucidate the ameliorating effect of 3-sucCA on MASH
Fourth, there is an important question, that is, what exactly is the use of 3-succinylcholic acid in humans and mice, and what is the principle behind it. They found that if there was less 3-succinylcholic acid in the stool, the more serious the liver problem would be, and conversely, if the more 3-succinylcholic acid in the stool, then the mucinophila ackermansia (AKK bacteria) would make better use of glucose and grow more to improve intestinal barrier damage and liver problems.
This is the heavyweight breakthrough of Changtao and the team, is it exciting?
From 2022 to this year, in three years, Changtao CNS has launched three times in a row!
In 2022, Nature, discovered the intestinal bacteria that degrade nicotine.
In 2023, Science, a new concept of fungal-derived host isozymes was proposed.
In 2024, "Cell", a new bacterial bile acid modification was discovered. Coupled with a series of papers published in academic journals such as Nature Medicine and Cell Metabolism, he has become an internationally influential expert in intestinal microbiome research.
In Warm Heart, this is the fifth CNS article by a local Chinese team this year. Through the continuous investment of our national and local governments, scientific research institutions and industry in the past years, especially through the efforts of scientists like Chang Tao who are not afraid of hardships and dare to innovate, China has formed a leading trend in some areas of intestinal research.
Thank you Changtao for the surprise you brought us, and congratulations to him and the team!
Conflict of Interest Statement
Conflict of Interest Statement
He is the co-founder and executive editor of iMeta journal, holds positions in professional institutions such as national societies, and serves as a university chair professor.
However, readers should be reminded that the company he founded and mainly works in, Beijing Warm Heart Biotechnology Research Institute Co., Ltd., is a for-profit commercial organization, and he also serves as chairman and director of this company and a number of affiliated companies.
In addition, he is also a consultant or consultant officially employed by Shanghai Pharmaceutical, H&H Group, Mengniu Group and other enterprises, and provides strategy, product and other consulting services for many other enterprises.
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In order to avoid and reduce the non-objectivity caused by conflicts of interest, Mr. Warmheart will take the following measures:
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