Peer-reviewedCC BY-NC-NDNature Catalysis
Transient dynamics of flavonoid metabolons tune chalcone synthase specificity
10 affiliations
- 1Graduate School of Engineering, Tohoku University, Sendai, Japan
- 2Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan
- 3Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
- 4Graduate School of Life Science, University of Hyogo, Ako-gun, Japan
- 5RIKEN SPring-8 Center, Sayo-gun, Japan
- 6Institute of Science and Engineering, Kanazawa University, Kanazawa, Japan
- 7Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan
- 8Nano Life Science Institute, Kanazawa University, Kanazawa, Japan
- 9Graduate School of Life Sciences, Tohoku University, Sendai, Japan
- 10Japan Synchrotron Radiation Research Institute (JASRI), Sayo-gun, Japan
Abstract
Cells achieve metabolic precision by assembling enzymes into dynamic complexes, but the regulatory mechanism of these metabolons is unclear. Here, we characterize the chalcone synthase (CHS)–chalcone isomerase-like protein (CHIL) complex, a key component of flavonoid metabolons. Whereas crystallography provides a static view, our analyses reveal that CHS undergoes rapid, reversible binding cycles with CHIL that regulate catalysis in real time. CHIL removes coenzyme A, an inhibitor of Claisen cyclization, transiently reshapes the CHS active site, and guides the tetraketide intermediate toward productive cyclization, thereby suppressing derailment byproducts. These findings demonstrate a previously unproven and generalizable regulatory effect in metabolons: guided active-site tuning via transient enzyme association. This concept enhances our understanding of metabolon function and opens new avenues for synthetic biology and metabolic engineering.
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BibTeX
@article{imaizumi2026transient,
title = {{Transient dynamics of flavonoid metabolons tune chalcone synthase specificity}},
author = {Riki Imaizumi and Toshiyuki Waki and Yoshikazu Hattori and Kohei Takeshita and Miru Sumita and Kazutomo Kawaguchi and Hiroyuki Kumeta and Kenichi Umeda and Kyohei Sato and Taro Yanai and Hiroaki Matsuura and Takeshi Yokoyama and Risa Omura and Kayo Nakatani and Naoki Sakai and Yukimura Kawagiwa and Yamato Doi and AOI YASUDA and 拓哉 中野 and Kaichi Uno and Kunihiro Yoshida and Misato Tsunashima and Tomohide Saio and Yoshikazu Tanaka and Seiji Takahashi and Noriyuki Kodera and Kunishige Kataoka and Masaki Yamamoto and Satoshi Yamashita and Tôru Nakayama},
journal = {Nature Catalysis},
year = {2026},
month = jun,
doi = {10.1038/s41929-026-01551-6},
url = {https://doi.org/10.1038/s41929-026-01551-6},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Transient dynamics of flavonoid metabolons tune chalcone synthase specificity
AU - Riki Imaizumi
AU - Toshiyuki Waki
AU - Yoshikazu Hattori
AU - Kohei Takeshita
AU - Miru Sumita
AU - Kazutomo Kawaguchi
AU - Hiroyuki Kumeta
AU - Kenichi Umeda
AU - Kyohei Sato
AU - Taro Yanai
AU - Hiroaki Matsuura
AU - Takeshi Yokoyama
AU - Risa Omura
AU - Kayo Nakatani
AU - Naoki Sakai
AU - Yukimura Kawagiwa
AU - Yamato Doi
AU - AOI YASUDA
AU - 拓哉 中野
AU - Kaichi Uno
AU - Kunihiro Yoshida
AU - Misato Tsunashima
AU - Tomohide Saio
AU - Yoshikazu Tanaka
AU - Seiji Takahashi
AU - Noriyuki Kodera
AU - Kunishige Kataoka
AU - Masaki Yamamoto
AU - Satoshi Yamashita
AU - Tôru Nakayama
PY - 2026
DA - 2026/06/15
JO - Nature Catalysis
DO - 10.1038/s41929-026-01551-6
UR - https://doi.org/10.1038/s41929-026-01551-6
AB - Cells achieve metabolic precision by assembling enzymes into dynamic complexes, but the regulatory mechanism of these metabolons is unclear. Here, we characterize the chalcone synthase (CHS)–chalcone isomerase-like protein (CHIL) complex, a key component of flavonoid metabolons. Whereas crystallography provides a static view, our analyses reveal that CHS undergoes rapid, reversible binding cycles with CHIL that regulate catalysis in real time. CHIL removes coenzyme A, an inhibitor of Claisen cyclization, transiently reshapes the CHS active site, and guides the tetraketide intermediate toward productive cyclization, thereby suppressing derailment byproducts. These findings demonstrate a previously unproven and generalizable regulatory effect in metabolons: guided active-site tuning via transient enzyme association. This concept enhances our understanding of metabolon function and opens new avenues for synthetic biology and metabolic engineering.
SN - 2520-1158
ER -