Generation of Stilbene Antimicrobials against Multiresistant Strains of Staphylococcus aureus through Biotransformation by the Enzymatic Secretome of Botrytis cinerea

Abstract

The biotransformation of a mixture of resveratrol and pterostilbene was performed by the protein secretome of Botrytis cinerea. Several reaction conditions were tested to overcome solubility issues and to improve enzymatic activity. Using MeOH as co-solvent, a series of unusual methoxylated compounds was generated. The reaction was scaled-up and the resulting mixture purified by semi-preparative HPLC-PDA-ELSD-MS. Using this approach, 15 analogues were isolated in one step. Upon full characterization by NMR and HRMS analyses, eight of the compounds were new. The antibacterial activities of the isolated compounds were evaluated in vitro against the opportunistic pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. The selectivity index (SI) was calculated based on cytotoxic assays performed against human liver carcinoma cells (HepG2) and human breast epithelial cell line (MCF10A). Some compounds revealed remarkable antibacterial activity against multidrug-resistant strains of S. aureus on the background of the moderate human cell line cytotoxicity.

Chemoenzymatic Synthesis of Original Stilbene Dimers Possessing Wnt Inhibition Activity in Triple-Negative Breast Cancer Cells Using the Enzymatic Secretome of Botrytis cinerea Pers.

“…Recently, we successfully used an enriched fraction of enzymes from fungi (“fungal secretome”) for the biotransformation of natural products to create complex derivative compounds with improved biological activity ( Gindro et al, 2017 ; Righi et al, 2020 ; Huber et al, 2021 ). The enzymatic diversity produced by fungi used for the degradation and/or transformation of various substrates has the potential to catalyze different chemical reactions ( Gindro et al, 2017 ).…”

“…It was also demonstrated that biotransformation reactions can be performed in the presence of high amounts of organic solvents ( Righi et al, 2020 ). These solvents can improve the solubility of substrates in aqueous media and also allow a relatively easy product recovery ( Klibanov, 2001 ).…”

Combination of Pseudo-LC-NMR and HRMS/MS-Based Molecular Networking for the Rapid Identification of Antimicrobial Metabolites From Fusarium petroliphilum

“…DAD detection was set between 190 and 500 nm. The system was controlled using MassLynx ® v4.2 (Waters), and the ESI and MS acquisition conditions were set according to the work of (Righi et al, 2020). For the metabolite profiling of the ethyl acetate extract, 3 µl was injected on an Acquity BEH C18 column (100 × 2.1 mm i.d., 1.7 µm; Waters, Milford, MA, United States).…”

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

“…The use of secretome takes advantage of the catalytic promiscuity of different enzymes ( Copley, 2003 ). This approach was successfully used for the generation of specific libraries of complex stilbene dimers with chiral carbons ( Gindro et al, 2017 ; Righi et al, 2020 ). Some of these compounds presented remarkable antifungal and antibacterial properties ( Gindro et al, 2017 ; Righi et al, 2020 ).…”

“…This approach was successfully used for the generation of specific libraries of complex stilbene dimers with chiral carbons ( Gindro et al, 2017 ; Righi et al, 2020 ). Some of these compounds presented remarkable antifungal and antibacterial properties ( Gindro et al, 2017 ; Righi et al, 2020 ). After having successfully applied this biotransformation process on stilbenes, we decided to use this methodology to another family of molecules, and phenylpropanoids were selected.…”