A discrete intermediate for the biosynthesis of both the enediyne core and the anthraquinone moiety of enediyne natural products

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dc.citation.articleNumbere2220468120
dc.citation.issueNumber9
dc.citation.journalTitleProceedings of the National Academy of Sciences
dc.citation.volumeNumber120
dc.contributor.authorBhardwaj, Minakshi
dc.contributor.authorCui, Zheng
dc.contributor.authorDaniel Hankore, Erome
dc.contributor.authorMoonschi, Faruk H.
dc.contributor.authorSaghaeiannejad Esfahani, Hoda
dc.contributor.authorKalkreuter, Edward
dc.contributor.authorGui, Chun
dc.contributor.authorYang, Dong
dc.contributor.authorPhillips, George N.
dc.contributor.authorThorson, Jon S.
dc.contributor.authorShen, Ben
dc.contributor.authorVan Lanen, Steven G.
dc.date.accessioned2023-03-10T19:04:16Z
dc.date.available2023-03-10T19:04:16Z
dc.date.issued2023
dc.description.abstractThe enediynes are structurally characterized by a 1,5-diyne-3-ene motif within a 9- or 10-membered enediyne core. The anthraquinone-fused enediynes (AFEs) are a subclass of 10-membered enediynes that contain an anthraquinone moiety fused to the enediyne core as exemplified by dynemicins and tiancimycins. A conserved iterative type I polyketide synthase (PKSE) is known to initiate the biosynthesis of all enediyne cores, and evidence has recently been reported to suggest that the anthraquinone moiety also originates from the PKSE product. However, the identity of the PKSE product that is converted to the enediyne core or anthraquinone moiety has not been established. Here, we report the utilization of recombinant E. coli coexpressing various combinations of genes that encode a PKSE and a thioesterase (TE) from either 9- or 10-membered enediyne biosynthetic gene clusters to chemically complement ΔPKSE mutant strains of the producers of dynemicins and tiancimycins. Additionally, 13C-labeling experiments were performed to track the fate of the PKSE/TE product in the ΔPKSE mutants. These studies reveal that 1,3,5,7,9,11,13-pentadecaheptaene is the nascent, discrete product of the PKSE/TE that is converted to the enediyne core. Furthermore, a second molecule of 1,3,5,7,9,11,13-pentadecaheptaene is demonstrated to serve as the precursor of the anthraquinone moiety. The results establish a unified biosynthetic paradigm for AFEs, solidify an unprecedented biosynthetic logic for aromatic polyketides, and have implications for the biosynthesis of not only AFEs but all enediynes.
dc.identifier.citationBhardwaj, Minakshi, Cui, Zheng, Daniel Hankore, Erome, et al.. "A discrete intermediate for the biosynthesis of both the enediyne core and the anthraquinone moiety of enediyne natural products." <i>Proceedings of the National Academy of Sciences,</i> 120, no. 9 (2023) PNAS: https://doi.org/10.1073/pnas.2220468120.
dc.identifier.digitalpnas-2220468120
dc.identifier.doihttps://doi.org/10.1073/pnas.2220468120
dc.identifier.urihttps://hdl.handle.net/1911/114507
dc.language.isoeng
dc.publisherPNAS
dc.rightsThis article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleA discrete intermediate for the biosynthesis of both the enediyne core and the anthraquinone moiety of enediyne natural products
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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