Noncatalytic chalcone isomerase-fold proteins in Humulus lupulus are auxiliary components in prenylated flavonoid biosynthesis

Proceedings of the National Academy of Sciences of the United States of America
Zhaonan BanGuodong Wang

Abstract

Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hops (Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two noncatalytic chalcone isomerase (CHI)-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase, and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a function of HlCHIL1 to bind DMX and naringenin chalcone to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis i...Continue Reading

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Citations

Sep 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Helge BerlandØyvind M Andersen
Sep 27, 2019·Journal of Experimental Botany·Rong NiAi-Xia Cheng
Mar 17, 2020·Annual Review of Plant Biology·Joseph R Jacobowitz, Jing-Ke Weng
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Aug 21, 2019·Frontiers in Plant Science·Keiko Yonekura-SakakibaraRyo Nakabayashi
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Jul 29, 2021·The Plant Journal : for Cell and Molecular Biology·Mehran Dastmalchi
Apr 25, 2019·Journal of Agricultural and Food Chemistry·Mark LevissonJules Beekwilder

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Methods Mentioned

BETA
RNAseq
confocal microscopy
two-hybrid
Y2H
co-IP
transgenic
thermal shift
PCR
transfection
fluorescence microscopy

Software Mentioned

Rad
BLAST
Maestro
TargetP
LigPrep
SiteMap
GraphPad Prism
Schrödinger
Hyper32
Bio

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