Researchers Decipher Enzyme Scissors of Intestinal Microbes
Intestinal bacteria utilise so-called beta-elimination to break down plant natural products and thus make them available to humans
Universal catalytic principle
The microbes use “enzymatic scissors” whose catalytic effect is based on so-called beta-elimination: a special type of reaction for the flexible cleavage of chemical bonds, including those of C-glycosides. The researchers succeeded in deciphering the enzyme’s mode of action at an atomic level and demonstrating the highly efficient cleavage of various glycosides. A manganese metal centre in the enzyme turned out to be essential for the cleavage process and its catalysis. “These enzymatic scissors are a universal catalytic principle that allows the natural product glycosides to be broken down regardless of the type of sugar linkage,” explains Bernd Nidetzky. The investigation of the enzymatic reaction mechanisms and the catalytic steps required not only high-resolution experimental methods such as protein crystallography but also computer-aided methods by which the dynamics of the biochemical processes could be mapped.
Bacteria living on plants also use enzyme scissors
The results were obtained as part of the “doc.funds” project CATALOX funded by the Austrian Science Fund and in co-operation with research groups at the Medical University of Graz and the University of Graz. As part of the investigations, the researchers were able to identify the evolutionary relationship of various enzyme scissors that cleave glycosides in a large number of microorganisms. “Bacteria in the intestinal flora have these enzyme scissors, as do a large group of plant-associated bacteria in nature,” says Bernd Nidetzky.
Bernd Nidetzky doubts that in the future the enzyme scissors mechanism can be used without the involvement of microorganisms, e.g. in food supplements, to improve the absorption of plant natural products. “It would be more conceivable to develop probiotics with microorganisms that have sufficient activity of these enzymes.”
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Johannes Bitter, Martin Pfeiffer, Annika J. E. Borg, Kirill Kuhlmann, Tea Pavkov-Keller, Pedro A. Sánchez-Murcia, Bernd Nidetzky; "Enzymatic β-elimination in natural product O- and C-glycoside deglycosylation"; Nature Communications, Volume 14, 2023-11-6
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