Planta Med 2022; 88(15): 1411-1412
DOI: 10.1055/s-0042-1758937
Short Lectures B: Biotechnology – Bioengineering

Short Lecture “Enzymatically engineered natural products as a source of invaluable bioactive compounds”

R Huber
1   School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland
2   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland
,
L Marcourt
1   School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland
2   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland
,
A Luscher
3   Department Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
,
A Koval
4   Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
,
N Hanna
5   Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland
,
J Nitschke
5   Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland
,
S Schnee
6   Mycology Group, Research Department Plant Protection, Agroscope, Nyon, Switzerland
,
E Michellod
6   Mycology Group, Research Department Plant Protection, Agroscope, Nyon, Switzerland
,
T Kohler
3   Department Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
,
V L Katanaev
4   Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
,
T Soldati
5   Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland
,
J-L Wolfender
1   School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland
2   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland
,
K Gindro
6   Mycology Group, Research Department Plant Protection, Agroscope, Nyon, Switzerland
,
E Ferreira Queiroz∗
1   School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland
2   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland
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Biotransformation of natural products (NPs) using enzymes represent an alternative to obtain bioactive compounds with original scaffolds and possible new modes of action. The concept of this approach is to start from abundant NPs to generate derivatives using chemoenzymatic reactions. In this context, instead of using a pure enzyme, we have successfully developed an original method based on the use of the enriched pool of enzymes secreted by a phytopathogenic fungus Botrytis cinerea to generate bioactive compounds [1]. The reaction mixtures are monitored by UHPLC-PDA-ELSD-HRMS metabolite profiling to highlight newly generated compounds. We found that the modulation of the reaction conditions, notably by increasing solvent concentration, led to the generation of unusual compounds. Promising reactions were selected and scaled up to generate sufficient amounts of biotransformed compounds. In most cases, it was possible to improve the structural diversity of the genuine NPs resulting in active compounds from inactive scaffolds. To rapidly isolate, characterize and study the biological activities of the generated compounds, the use of high-resolution preparative chromatographic methods was mandatory. For this we develop efficient targeted isolation methods based chromatographic gradient transfer and dry load. Chiral separation was used to check whether stereochemistry could impact biological properties. This approach resulted in a library of more than 170 compounds, some of which show interesting antibacterial properties, and anti Wnt activity in TNBC cells [2], [3], [4]. The possibilities and limitations of this technology will be illustrated by recent investigations performed in our laboratory.



Publikationsverlauf

Artikel online veröffentlicht:
12. Dezember 2022

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  • References

  • 1 Queiroz EF, Gindro K. Improve the chemical biodiversity of natural products for drug discovery by fungal secretome-assisted biotransformation. The Swiss National Science Foundation provided financial support for this project. Grant 205321_182438/1.
    PubMed
  • 2 Righi D, Huber R, Koval A. et al. Generation of stilbene antimicrobials against multiresistant strains of Staphylococcus aureus through biotransformation by the enzymatic secretome of Botrytis cinerea. J Nat Prod 2020; 83: 2347-2356
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    CrossrefPubMedSuche in Google Scholar