キノコの酸化酵素を用いた有用反応探索 〜カワラタケP450の潜在機能を迅速解明〜

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2025-05-09 九州大学

キノコの酸化酵素を用いた有用反応探索 〜カワラタケP450の潜在機能を迅速解明〜

九州大学の研究チームは、脳内の免疫細胞であるミクログリアが、細胞外に放出されるヌクレオチドであるUDP(ウリジン二リン酸)を感知し、貪食(不要物の取り込み)を促進する新たなメカニズムを解明しました。具体的には、ミクログリアに発現するP2Y6受容体がUDPを検知すると、細胞内のカルシウム濃度が上昇し、貪食能が飛躍的に増強されることが確認されました。この発見は、神経変性疾患や脳損傷後の治療法開発において、ミクログリアの機能を調節する新たなターゲットとなる可能性があります。

<関連情報>

白色腐朽性担子菌Trametes versicolor由来チトクロームP450モノオキシゲナーゼの機能解析:CYP502B15はカジナン型セスキテルペノイドを装飾する Functional analysis of cytochrome P450 monooxygenases from the white-rot basidiomycete Trametes versicolor: CYP502B15 decorates cadinane-type sesquiterpenoids

Hirofumi Ichinose, Megumu Honda, Tsuyoshi Isogai, Chen Chen, Takuya Kitaoka
Enzyme and Microbial Technology  Available online: 21 April 2025
DOI:https://doi.org/10.1016/j.enzmictec.2025.110658

Highlights

  • Cytochrome P450 monooxygenases from Trametes versicolor.
  • Library of cytochrome P450 monooxygenases and their functions.
  • Hydroxylation of γ-cadinene and epicubenol by CYP502B15.

Abstract

Cytochrome P450 monooxygenases (P450) play crucial roles in the diversification of secondary metabolic systems in living organisms. Basidiomycetes produce a wide variety of natural products as secondary metabolites, with their relevance to pharmaceutical and agricultural applications garnering significant interest. Thus, the functional characterization of fungal P450s is essential for basic and applied research of basidiomycetes. We herein describe the identification and functional characterization of P450 in the white-rot basidiomycete Trametes versicolor (TvCYP). A total of 182 TvCYP genes were identified in the T. versicolor genome. Moreover, 145 cDNAs encoding possible mature open reading frames were isolated/generated. Furthermore, we constructed a library of TvCYPs using a yeast expression system that allowed for the semi-comprehensive screening of latent TvCYP functions. Notably, we used this library to identify TvCYPs responsible for the metabolism of cadinane-type sesquiterpenoids. CYP502B15 was revealed to have significant activities against γ-cadinene and epicubenol. On the basis of NMR and X-ray crystal structure experiments, CYP502B15 was observed to catalyze the 3α-hydroxylation of γ-cadinene and epicubenol. To the best of our knowledge, this is the first report of the identification of basidiomycetous P450s responsible for the metabolism of cadinane-type sesquiterpenoids.

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