Efficient monooxygenase-catalyzed piceatannol production: Application of cyclodextrins for reducing product inhibition

Abstract

Piceatannol is a rare, costly plant-based stilbene derivative and exhibits various health-enhancing properties. Recently, we demonstrated that piceatannol could be produced from resveratrol through site-selective hydroxylation using Escherichia coli cells expressing the monooxygenase HpaBC. However, piceatannol production ceased at approximately 25 mM, even when sufficient levels of the substrate resveratrol remained in the reaction mixture. In this study, we found that high concentrations (>20-25 mM) of piceatannol significantly inhibited the HpaBC-catalyzed reaction. Cyclodextrins (CDs) reportedly encapsulate various hydrophobic compounds. We found that the addition of β-CD or γ-CD to the reaction mixture reduced the inhibition caused by the product piceatannol. The effects of β-CD on piceatannol production were more pronounced than those of γ-CD at high concentrations of the substrate resveratrol and CDs. The production of piceatannol reached 49 mM (12 g L^-1) in the presence of β-CD, a level twice that achieved in the absence of β-CD. The technique described here might be applicable to the bioproduction of other stilbenes and structurally related compounds.

Keywords: Cyclodextrin; Monooxygenase; Piceatannol; Product inhibition; Resveratrol; Whole-cell catalyst.