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Researchers at TU Graz Decipher Enzyme Scissors of Intestinal Microbes

11/29/2023 | TU Graz news | Research

By Philipp Jarke

Flavonoids & Co: Microorganisms in the human gut utilise so-called beta-elimination to break down plant natural products and thus make them available to humans.

Intestinal microbes (symbolic representation). Image source: Adobe Stock/Ruslan Batiuk

Fruit and vegetables contain a variety of plant natural products such as flavonoids, which give fruits their colour and are said to have health-promoting properties. Most plant natural products occur in nature as glycosides, i.e. chemical compounds with sugars. In order for humans to absorb the healthy plant natural products, the sugar must be split off in the intestine. Microorganisms in the intestinal flora help to speed up the process. So-called C-glycosides, i.e. plant natural products with a carbon-based bond to a sugar, would even be practically indigestible without the intestinal microbes (e.g. nothofagin in rooibos tea). A research team led by Johannes Bitter, Martin Pfeiffer and Bernd Nidetzky from the Institute of Biotechnology and Biochemical Engineering at Graz University of Technology (TU Graz) has now been able to determine which tool the intestinal bacteria use to cleave glycosides and how it works.

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.”

This research area is anchored in the Field of Expertise “Human & Biotechnology“, one of the five strategic research areas of TU Graz.

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Enzymatic β-elimination in natural product O- and C-glycoside deglycosylation. Nature Communications 14, 7123 (2023).

Johannes Bitter, Martin Pfeiffer, Annika J. E. Borg, Kirill Kuhlmann, Tea Pavkov-Keller, Pedro A. Sánchez-Murcia & Bernd Nidetzky

DOI: https://doi.org/10.1038/s41467-023-42750-0


Univ.-Prof. Dipl.-Ing. Dr.techn. Dr.h.c.
TU Graz | Institute of Biotechnology and Biochemical Engineering
Phone: +43 316 873 8400, bernd.nidetzkynoSpam@tugraz.at

Johannes BITTER
Dipl.-Ing. BSc
Phone: +43 316 873 8408, j.bitternoSpam@tugraz.at

Dipl.-Ing. Dr.techn. BSc
Phone: +43 316 873 8415, martin.pfeiffernoSpam@tugraz.at