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Cited by 6Plant Gene Expression AnalysisPlant biochemistry and biosynthesisBiochemical and biochemical processes

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Transient dynamics of flavonoid metabolons tune chalcone synthase specificity

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Imaizumi, Riki, Waki, Toshiyuki, Hattori, Yoshikazu, Takeshita, Kohei, Sumita, Miru, Kawaguchi, Kazutomo, Kumeta, Hiroyuki, Umeda, Kenichi, Sato, Kyohei, Yanai, Taro, Matsuura, Hiroaki, Yokoyama, Takeshi, Omura, Risa, Nakatani, Kayo, Sakai, Naoki, Kawagiwa, Yukimura, Doi, Yamato, Yasuda, Aoi, Nakano, Takuya, Uno, Kaichi, Yoshida, Kunihiro, Tsunashima, Misato, Saio, Tomohide, Tanaka, Yoshikazu, Takahashi, Seiji, Kodera, Noriyuki, Kataoka, Kunishige, Yamamoto, Masaki, Yamashita, Satoshi, Nakayama, Toru·2026·Nature Catalysis
DOI 10.1038/s41929-026-01551-6

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Abstract

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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Metadata

Authors
Imaizumi, R., Waki, T., Hattori, Y., Takeshita, K., Sumita, M., Kawaguchi, K., Kumeta, H., Umeda, K., Sato, K., Yanai, T., Matsuura, H., Yokoyama, T., Omura, R., Nakatani, K., Sakai, N., Kawagiwa, Y., Doi, Y., Yasuda, A., Nakano, T., Uno, K., Yoshida, K., Tsunashima, M., Saio, T., Tanaka, Y., Takahashi, S., Kodera, N., Kataoka, K., Yamamoto, M., Yamashita, S., & Nakayama, T.
Affiliations
  • Kanazawa University (JP)
  • Tohoku University (JP)
  • Institute of Advanced Medical Sciences, Tokushima University (JP)
  • University of Hyogo (JP)
  • Hokkaido University (JP)
  • Japan Synchrotron Radiation Research Institute (JP)
  • SPring-8 (JP)
Corresponding author
Yamashita, Satoshi
ORCID
Venue
Nature Catalysis
Publisher
Springer Science and Business Media LLC
Published
2026-06-15
Volume
9
Issue
6
Pages
630-644
ISSN
2520-1158 (ISSN-L)
DOI
10.1038/s41929-026-01551-6
OpenAlex
W7164836963
Cited by
6
References
1
Citations by year
2026: 6
FWCI
12.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Catalysis (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
Funders
  • MEXT | Japan Society for the Promotion of Science (23H05470, 18H03938, 21J22186, 22KJ1466, 24K23286, 20K15448, 25H01418, 21H02115)
  • Bio-SPMs Collaborative Research of the WPI Nano Life Science Institute
  • Japan Agency for Medical Research and Development (JP20am0101070 (support number 1841))
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant Gene Expression Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Biochemical and biochemical processes
Keywords
chalcone synthase, flavonoid biosynthesis, coenzyme A, enzyme specificity, metabolic regulation

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