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<p>Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(<i>L</i>-Val-<i>L</i>-His) and cyclo-(<i>L</i>-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding <i>C</i>2-regular and <i>C</i>5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-<i>C</i>-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.</p>

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Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月2日

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  • Wenxue Wang,
  • Peng Wang,
  • Chuanteng Ma,
  • Kang Li,
  • Zian Wang,
  • Yuting Liu,
  • Lu Wang,
  • Guojian Zhang,
  • Qian Che,
  • Tianjiao Zhu,
  • Yuzhong Zhang,
  • Dehai Li

摘要

Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.