在真菌美基生物合成中的异构非血型铁酶
Xinyang Li1, Takayoshi Awakawa1,2, Takahiro Mori1,2,3
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|December 9, 2021
概括
海洋真菌Talaromyces purpureogenus产生一种不寻常的六环性美类物质,称为塔拉罗米奥利德. 研究人员阐明了它们的生物合成基因集群 (tlxA-J),并发现了催化关键氧化步骤的新型非血铁 (NHI) 酶异构体.
科学领域:
- 生物化学
- 自然产品化学
- 分子生物学
背景情况:
- 塔拉罗米奥利德是从海洋真菌Talaromyces purpureogenus中分离出来的复杂的六环甲.
- 这些化合物具有独特的 (3R) - 6 - 烯和4,5 - 烯基结构.
研究的目的:
- 识别和描述负责塔拉罗米奥利德生产的生物合成基因群.
- 阐明复杂的塔拉罗米奥利德支架形成的酶机制.
- 研究非血铁 (NHI) 酶异构体在二次代谢物生物合成中的新型催化作用.
主要方法:
- 在Aspergillus中假定生物合成基因群 (tlxA-J) 的异构表达.
- 在体外酶测试以确定单个和组合酶的催化活性.
- 基于CRISPR-Cas9的基因失活,以确认基因功能.
- 进行X射线结构分析和位点定向突变,以了解酶结构功能关系.
主要成果:
- 生物合成基因集群tlxA-J被确定并进行了功能性特征.
- 发现NHI酶的异构体TlxJ-TlxI催化了三个氧化步骤,包括一个关键的逆醇反应,促进了4,5-二氧化物骨的形成.
- 另一种NHI异构体TlxA-TlxC和TlxB参与了随后的化和乙化步骤,以获得最终产品.
- 结构分析提供了TlxJ-TlxI异构体的形成和催化机制的见解.
结论:
- 这项研究揭示了塔拉罗米奥利德的完整生物合成途径,突出了NHI酶异构体的关键作用.
- 这是第一份报告,证明两种NHI蛋白在二次代谢物生物合成中形成功能性异构体.
- 在二次代谢物生物合成中创建功能性氧酶结构的新方法.
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