Rational Design of Resveratrol O-methyltransferase for the Production of Pinostilbene

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dc.contributor.authorHerrera, Daniela P.
dc.contributor.authorChanique, Andrea M.
dc.contributor.authorMartinez-Marquez, Ascension
dc.contributor.authorBru-Martinez, Roque
dc.contributor.authorKourist, Robert
dc.contributor.authorParra, Loreto P.
dc.contributor.authorSchuller, Andreas
dc.date.accessioned2025-01-20T22:21:54Z
dc.date.available2025-01-20T22:21:54Z
dc.date.issued2021
dc.description.abstractPinostilbene is a monomethyl ether analog of the well-known nutraceutical resveratrol. Both compounds have health-promoting properties, but the latter undergoes rapid metabolization and has low bioavailability. O-methylation improves the stability and bioavailability of resveratrol. In plants, these reactions are performed by O-methyltransferases (OMTs). Few efficient OMTs that monomethylate resveratrol to yield pinostilbene have been described so far. Here, we report the engineering of a resveratrol OMT from Vitis vinifera (VvROMT), which has the highest catalytic efficiency in di-methylating resveratrol to yield pterostilbene. In the absence of a crystal structure, we constructed a three-dimensional protein model of VvROMT and identified four critical binding site residues by applying different in silico approaches. We performed point mutations in these positions generating W20A, F24A, F311A, and F318A variants, which greatly reduced resveratrol's enzymatic conversion. Then, we rationally designed eight variants through comparison of the binding site residues with other stilbene OMTs. We successfully modified the native substrate selectivity of VvROMT. Variant L117F/F311W showed the highest conversion to pinostilbene, and variant L117F presented an overall increase in enzymatic activity. Our results suggest that VvROMT has potential for the tailor-made production of stilbenes.
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms22094345
dc.identifier.eissn1422-0067
dc.identifier.urihttps://doi.org/10.3390/ijms22094345
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94663
dc.identifier.wosidWOS:000650399600001
dc.issue.numero9
dc.language.isoen
dc.revistaInternational journal of molecular sciences
dc.rightsacceso restringido
dc.subjectenzyme engineering
dc.subjectO-methyltransferases
dc.subjectpinostilbene
dc.subjectprotein models
dc.subjectsubstrate selectivity
dc.subjectstilbenes
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRational Design of Resveratrol O-methyltransferase for the Production of Pinostilbene
dc.typeartículo
dc.volumen22
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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