Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins

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dc.citation.articleNumber4158
dc.citation.journalTitleNature Communications
dc.citation.volumeNumber12
dc.contributor.authorLiu, Zhiwen
dc.contributor.authorZhao, Fanglong
dc.contributor.authorZhao, Boyang
dc.contributor.authorYang, Jie
dc.contributor.authorFerrara, Joseph
dc.contributor.authorSankaran, Banumathi
dc.contributor.authorVenkataram Prasad, B.V.
dc.contributor.authorKundu, Biki Bapi
dc.contributor.authorPhillips, George N.Jr.
dc.contributor.authorGao, Yang
dc.contributor.authorHu, Liya
dc.contributor.authorZhu, Tong
dc.contributor.authorGao, Xue
dc.date.accessioned2021-07-30T15:21:25Z
dc.date.available2021-07-30T15:21:25Z
dc.date.issued2021
dc.description.abstractPrenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.
dc.identifier.citationLiu, Zhiwen, Zhao, Fanglong, Zhao, Boyang, et al.. "Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins." <i>Nature Communications,</i> 12, (2021) Springer Nature: https://doi.org/10.1038/s41467-021-24421-0.
dc.identifier.digitals41467-021-24421-0
dc.identifier.doihttps://doi.org/10.1038/s41467-021-24421-0
dc.identifier.urihttps://hdl.handle.net/1911/111050
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleStructural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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