2026-07-02 京都大学
本研究で開発した新規酵素探索手法の概略。Created with BioRender.com
＜関連情報＞
- https://www.kyoto-u.ac.jp/ja/research-news/2026-07-02
- https://www.nature.com/articles/s41929-026-01560-5
擬似天然プレニル化ペプチドを多様化するためのペプチドプレニルトランスフェラーゼの迅速スクリーニングプラットフォーム Rapid screening platform for peptide prenyltransferases to diversify pseudo-natural prenylated peptides
Sumika Inoue (井上 澄香),Shunya Matsushita (松下 峻也),Sayaka Ito (伊藤 清香),Marin Yokomine (横峰 真琳),Masayuki Satake (佐竹 真幸),Chikako Okada (岡田 千佳子),Keisuke Hamada (濱田 恵輔),Yuchen Zhang (張 宇琛),Risa Ohta (太田 利紗),Taro Shiraishi (白石 太郎),Hiroaki Suga (菅 裕明),Masahiro Okada (岡田 正弘),Toru Sengoku (仙石 徹) & Yuki Goto (後藤 佑樹)
Nature Catalysis Published:01 July 2026
DOI:https://doi.org/10.1038/s41929-026-01560-5
Abstract
Peptide lipidation can enhance stability and permeability, yet biocatalysts for late-stage, site- and mode-selective modification remain limited. Here we established a streamlined activity-profiling system that rapidly assesses peptide-prenylating activities using an artificial substrate set. Screening 19 recombinant, putative cyanobactin prenyltransferases (PTases) uncovered 14 active enzymes with diverse catalytic properties, including five previously unreported modes of prenylation, bifunctionality towards Trp/Tyr and expanded donor utilization such as farnesylation. Co-crystal structures of seven PTases reveal how subtle active-site changes enable dual substrate recognition and accommodation of bulkier donors, highlighting the evolutionary diversification of catalytic functions. The enzymes tolerate non-native substrates, enabling late-stage, site- and mode-selective lipidation to construct pseudo-natural peptides. Together, these findings expand the enzymatic and mechanistic landscape of cyanobactin PTases, enlarging their functional repertoire and revealing the structural principles that govern the diversification of peptide prenylation chemistry.
