Optimize, Modulate, and Scale-up Resveratrol and Resveratrol Dimers Bioproduction in Vitis labrusca L. Cell Suspension from Flasks to 20 L Bioreactor.

Resveratrol and its oligomers are biologically active compounds. This work brings new insights for the bioproduction of trans-resveratrol with three dimers, pallidol, trans-ε-viniferin, and trans-δ-viniferin, in cell suspension of Vitis labrusca. Conditions of elicitation by methyl jasmonate were optimized for the production of stilbenes using statistical design of experiment. Bio-production of stilbenes was scaled-up to 5 L and in these conditions, trans-resveratrol concentrations reached 237 mg/L, and for pallidol 114 mg/L. The comparison of different elicitation modes (different elicitors, combination with cyclodextrins or adsorbent resin) allowed to reach particularly high concentrations of target molecules: Resveratrol 6.14 g/L, pallidol 0.90 g/L, δ-viniferin 0.54 g/L, and ε-viniferin 0.50 g/L. Scale-up to 20 L-stirring-bioreactor gave similar growth rates to those observed in shake flask culture, with a high production of resveratrol (4.23 g/L) and δ-viniferin (0.76 g/L). This work provides new strategies for the production of stilbenes in plant cell suspension for biological and commercial evaluation.