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Structure-guided switching of carbocation quenching in sesquiterpene synthases for accessing aromadendrane and guaiane frameworks

delete2026-03-01
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PRE
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A
Atsushi Suwa
S
Shusuke Sato
M
Minami, Atsushi *
DOI：10.1093/bulcsj/uoag032delete
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Abstract

Abstract

En 中文
The extraordinary structural diversity of terpenoid natural products arises from enzyme-controlled carbocation rearrangements during cyclization. Understanding how sesquiterpene synthases (STSs) control these reactive intermediates is a key challenge in enzymatic catalysis. In this study, we demonstrate the rational control of carbocation-quenching pathways in aromadendrane-type STSs through structure-guided mutagenesis. Mutational analysis of 2 key residues (S75 and T95) in CpSTS9 enabled us to switch the product profile from viridiflorol (via water quenching) to 9-alloaromadendrene (via deprotonation), and further to gamma-gurjunene with an altered carbon-skeleton framework. Structural modeling indicates that subtle reshaping of the active site redirects the cyclization and quenching pathways. These results establish a mechanism for modulating the cyclization pathway and provide a basis for designing artificial enzymes capable of controlling complex carbon-skeleton formation.
Keywords:
functional modulation
mutational studies
sesquiterpene synthase

Journal

Bulletin of the Chemical Society of Japan cover
Bulletin of the Chemical Society of Japan
IF:
3.8
Papers:
9.0K
Citations:
1.1W

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