Chemoenzymatic Synthesis of Complex Phenylpropanoid Derivatives by the Botrytis cinerea Secretome and Evaluation of Their Wnt Inhibition Activity

Robin Huber; Laurence Marcourt; Alexey Koval; Sylvain Schnee; Davide Righi; Emilie Michellod; Vladimir L Katanaev; Jean-Luc Wolfender; Katia Gindro; Emerson Ferreira Queiroz

doi:10.3389/fpls.2021.805610

Chemoenzymatic Synthesis of Complex Phenylpropanoid Derivatives by the Botrytis cinerea Secretome and Evaluation of Their Wnt Inhibition Activity

Front Plant Sci. 2022 Jan 13:12:805610. doi: 10.3389/fpls.2021.805610. eCollection 2021.

Authors

Robin Huber^{1

2}, Laurence Marcourt^{1

2}, Alexey Koval³, Sylvain Schnee⁴, Davide Righi^{1

2}, Emilie Michellod⁴, Vladimir L Katanaev^{3

5}, Jean-Luc Wolfender^{1

2}, Katia Gindro⁴, Emerson Ferreira Queiroz^{1

2}

Affiliations

¹ School of Pharmaceutical Sciences, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.
² Institute of Pharmaceutical Sciences of Western Switzerland, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.
³ Department of Cell Physiology and Metabolism, Translational Research Centre in Oncohaematology, Faculty of Medicine, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.
⁴ Mycology Group, Research Department Plant Protection, Agroscope, Nyon, Switzerland.
⁵ School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.

Abstract

In this study, a series of complex phenylpropanoid derivatives were obtained by chemoenzymatic biotransformation of ferulic acid, caffeic acid, and a mixture of both acids using the enzymatic secretome of Botrytis cinerea. These substrates were incubated with fungal enzymes, and the reactions were monitored using state-of-the-art analytical methods. Under such conditions, a series of dimers, trimers, and tetramers were generated. The reactions were optimized and scaled up. The resulting mixtures were purified by high-resolution semi-preparative HPLC combined with dry load introduction. This approach generated a series of 23 phenylpropanoid derivatives, 11 of which are described here for the first time. These compounds are divided into 12 dimers, 9 trimers (including a completely new structural scaffold), and 2 tetramers. Elucidation of their structures was performed with classical spectroscopic methods such as NMR and HRESIMS analyses. The resulting compound series were analyzed for anti-Wnt activity in TNBC cells, with several derivatives demonstrating specific inhibition.

Keywords: Botrytis cinerea; Wnt inhibition; biotransformation; chemoenzymatic synthesis; dry load introduction; enzymatic secretome; high-resolution semi-preparative HPLC; phenylpropanoids.