The molecular landscape of bitter substances remains largely uncharted, but a new study has pushed its boundaries further. Researchers from the Leibniz Institute for Food Systems Biology at the Technical University of Munich in Freising, along with colleagues from the Leibniz Institute of Plant Biochemistry in Halle (Saale), have isolated three new bitter compounds from the non-toxic mushroom Amaropostia stiptica. Their findings shed light on how these substances interact with human bitter taste receptors.
Published in the Journal of Agricultural and Food Chemistry, the study not only identifies one of the most potent bitter compounds known to date, but also contributes significantly to our understanding of natural bitterness and its relevance to food and health science.
Currently, the BitterDB database lists over 2,400 known bitter molecules, with around 800 of these linked to at least one human bitter taste receptor. However, the majority of documented bitter substances come from flowering plants or synthetic sources. Bitter molecules originating from fungi, animals, or bacteria remain underrepresented.
Scientists believe bitter taste receptors evolved to help humans avoid harmful substances. Yet, the relationship is far from straightforward—not all bitter substances are dangerous, and not all toxins taste bitter. For example, the deadly death cap mushroom contains lethal toxins that lack bitterness. This paradox raises questions about how bitter receptors function and why they are present not only in the mouth but also throughout the body—in organs like the stomach, intestines, heart, lungs, and even on certain blood cells.
“Comprehensive data on bitter compounds and their corresponding receptors could help us better understand these mysteries,” said Maik Behrens, who leads a research group at the Leibniz Institute in Freising. “With robust datasets, we can use systems biology to predict how new bitter compounds might interact with different receptors, both in food science and in relation to our internal physiology.”
As part of their joint research effort, Behrens' team partnered with Norbert Arnold's group in Halle to study the Bitter Bracket mushroom (Amaropostia stiptica), known for its intensely bitter taste despite being non-toxic.
Using advanced analytical techniques, Arnold’s team isolated and identified the structures of three previously unknown bitter compounds. Behrens’ lab then used a cellular testing system to evaluate how these molecules activate the approximately 25 known human bitter taste receptors.
https://github.com/BrentGNT/Arch2
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https://github.com/AidenBMT/Wmumd
https://github.com/BlakeTNS/S2ugm
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https://github.com/BrodyTNN/Cscofps
https://github.com/CalebSNT/Bmumg
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One compound stood out—oligoporin D. This substance proved to be extraordinarily potent, activating the TAS2R46 receptor at concentrations as low as 63 nanograms per liter. To put that into perspective, one gram of oligoporin D would need to be dissolved in about 106 bathtubs of water to reach the same concentration. That’s roughly the mass of a knife-tip’s worth of baking soda spread across more than a hundred bathtubs.
“Our findings enhance the current understanding of the structural diversity and receptor interactions of natural bitter compounds,” said Behrens. “In the long run, such insights could support the development of functional foods that not only taste good but also promote digestive health and satiety.”
The discovery of these powerful new bitter compounds opens the door to new applications in both nutrition and medicine, offering a deeper understanding of how our bodies interact with the chemical world—sometimes in the subtlest of concentrations.