Scholarlink

<p>The marine bacterial flavoenzymes Clz9 and Tcz9 can process cannabigerolic acid to the minor cannabinoid, cannabichromenic acid (CBCA); however, the mechanistic details of this extrinsic transformation are still obscure. Here we report a thorough analysis of CBCA formation by Clz9 and Tcz9 through high-resolution crystallographic characterization, biochemical analysis and spectroscopic interrogation. Our work reveals that Clz9 and Tcz9 use different biochemical mechanisms from <i>Cannabis</i> cyclases and each other in their production of CBCA. Collection of a high-resolution substrate-bound structure provides additional key insights into how active site architecture affects substrate binding and stereoselectivity. Engineering approaches improve the stereoselectivity of CBCA formation by Clz9 and Tcz9, providing access to (<i>R</i>) and (<i>S</i>)-CBCA. Collectively, our work advances understanding of enzymatic cannabinoid formation and cements Clz9 and Tcz9 as two unique members of the BBE-like enzyme family with encouraging potential for biocatalytic cannabinoid production applications.</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

Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes

  • 期刊论文

  • 发表日期：

    2026年7月7日

查看全文
  • Anna C. Love,
  • Harshverdhan Sirohi,
  • Felix M. Hubert,
  • Ying-Chieh Kao,
  • Daniel E. Quinnell,
  • Tian Lan,
  • Ryan Gappy,
  • Marissa Sheehy,
  • Jonathan Hsu,
  • Adrian Lee,
  • Liana Zangwill,
  • Timothy Chang,
  • Bruce A. Palfey,
  • Geoffrey Chang,
  • Bradley S. Moore

摘要

The marine bacterial flavoenzymes Clz9 and Tcz9 can process cannabigerolic acid to the minor cannabinoid, cannabichromenic acid (CBCA); however, the mechanistic details of this extrinsic transformation are still obscure. Here we report a thorough analysis of CBCA formation by Clz9 and Tcz9 through high-resolution crystallographic characterization, biochemical analysis and spectroscopic interrogation. Our work reveals that Clz9 and Tcz9 use different biochemical mechanisms from Cannabis cyclases and each other in their production of CBCA. Collection of a high-resolution substrate-bound structure provides additional key insights into how active site architecture affects substrate binding and stereoselectivity. Engineering approaches improve the stereoselectivity of CBCA formation by Clz9 and Tcz9, providing access to (R) and (S)-CBCA. Collectively, our work advances understanding of enzymatic cannabinoid formation and cements Clz9 and Tcz9 as two unique members of the BBE-like enzyme family with encouraging potential for biocatalytic cannabinoid production applications.