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Qualitative Metabolomics-Based Characterization of a Phenolic UDP-Xylosyltransferase with a Broad Substrate Spectrum from Lentinus brumalis

Summary

This research discovered a new enzyme from wood-decaying fungi that can modify various chemical compounds by adding sugar molecules to them. This discovery is significant for developing better ways to produce medicines and other valuable chemicals. The enzyme works by making toxic compounds less harmful, which is similar to how our bodies process medications. Impacts on everyday life: • Could lead to more efficient and environmentally friendly ways to produce medicines • May help develop new methods for improving drug properties like solubility and stability • Demonstrates nature’s potential as a source of useful industrial tools • Could contribute to more sustainable chemical manufacturing processes • May help in developing new ways to detoxify harmful compounds in the environment

Background

Biocatalysts have become an attractive alternative to conventional chemical catalysts, but narrow substrate scopes have been a critical bottleneck in using biocatalysts in chemical synthesis. Wood-decaying fungi are hypothesized to possess promiscuous enzymes for detoxifying antifungal phytochemicals remaining in dead plant bodies, which could be useful as biocatalysts.

Objective

To employ mass spectrometry-based untargeted metabolomics analysis to identify fungal enzymes with broad substrate specificity by analyzing the catalytic activities of wood-decaying fungi against phytochemicals. The study aimed to discover and characterize enzymes that could serve as promising biocatalysts.

Results

The analysis identified diverse reactivities by the tested fungal species, particularly focusing on O-xylosylation of multiple phenolics by Lentinus brumalis. A UDP-glycosyltransferase designated UGT66A1 was identified and validated as an enzyme catalyzing O-xylosylation with broad substrate specificity. The enzyme showed activity against various phenolic compounds including synthetic molecules, and demonstrated significant preference for UDP-xylose as a sugar donor compared to UDP-glucose.

Conclusion

The study successfully demonstrated the efficiency of computational mass spectrometry-based untargeted metabolomics for discovering enzymes with broad substrate specificity from wood-decaying fungi. The identified enzyme UGT66A1 represents a promising biocatalyst for glycosylation of bioactive molecules, with potential applications in drug development and chemical synthesis.
  • Published in:Proceedings of the National Academy of Sciences of the United States of America,
  • Study Type:Laboratory Research,
  • Source: 10.1073/pnas.2301007120
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