Scholarlink

<p>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.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Rapid screening platform for peptide prenyltransferases to diversify pseudo-natural prenylated peptides

  • 期刊论文

  • 发表日期：

    2026年7月1日

查看全文
  • Sumika Inoue,
  • Shunya Matsushita,
  • Sayaka Ito,
  • Marin Yokomine,
  • Masayuki Satake,
  • Chikako Okada,
  • Keisuke Hamada,
  • Yuchen Zhang,
  • Risa Ohta,
  • Taro Shiraishi,
  • Hiroaki Suga,
  • Masahiro Okada,
  • Toru Sengoku,
  • Yuki Goto

摘要

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.