谢萌, 潘英妮, 李宁, 訾佳辰. 修饰芳香族化合物的异戊烯基转移酶研究进展J. 药学学报, 2025, 60(3): 573-586. DOI: 10.16438/j.0513-4870.2024-1067
引用本文: 谢萌, 潘英妮, 李宁, 訾佳辰. 修饰芳香族化合物的异戊烯基转移酶研究进展J. 药学学报, 2025, 60(3): 573-586. DOI: 10.16438/j.0513-4870.2024-1067
XIE Meng, PAN Ying-ni, LI Ning, ZI Jia-chen. Advances in prenyltransferases research for modifying aromatic natural productsJ. Acta Pharmaceutica Sinica, 2025, 60(3): 573-586. DOI: 10.16438/j.0513-4870.2024-1067
Citation: XIE Meng, PAN Ying-ni, LI Ning, ZI Jia-chen. Advances in prenyltransferases research for modifying aromatic natural productsJ. Acta Pharmaceutica Sinica, 2025, 60(3): 573-586. DOI: 10.16438/j.0513-4870.2024-1067

修饰芳香族化合物的异戊烯基转移酶研究进展

Advances in prenyltransferases research for modifying aromatic natural products

  • 摘要: 具有异戊烯基取代的芳香族天然产物(prenylated aromatic natural products, PANPs) 广泛存在于自然界中。由于核心骨架的变化(香豆素、木脂素、苯甲酸/苯甲醇、黄酮、氧杂蒽酮、蒽醌和芳香生物碱等) 以及异戊烯基的类型、取代位置和是否环合的差别, PANPs展现出丰富的结构多样性。多样的结构也赋予了PANPs多样的活性, 例如抗菌、抗氧化、抗肿瘤和消炎镇痛等作用。因此, PANPs具有很好的药物开发价值。对于当归、前胡及补骨脂等中药材, PANPs是其重要的药效物质。值得注意的是, 异戊烯基往往是关键药效团。根据亲缘关系以及结构特征, PANPs生物合成途径中的芳香族异戊烯基转移酶(aromatic prenyltransferases, aPTs) 可分为膜结合(membrane-bound) aPTs (UbiA型)、具有PT桶状(PT barrel) 结构的可溶性aPTs (ABBA型和DMATS型) 以及类似萜合酶的aPTs。本文综述了近10年发现的94个不同类型的aPTs, 重点总结了它们的底物选择性、区域选择性、进化关系及结构特征, 为新颖aPTs的发现、改造, 以及活性PANPs的结构修饰和生物制造提供思路。

     

    Abstract: Prenylated aromatic natural products (PANPs) are widely distributed in nature. PANPs exhibit a great structural diversity due to their various core scaffolds (coumarin, lignan, benzoic acid/benzyl alcohol, flavonoid, xanthone, anthraquinone, and aromatic alkaloid, etc.) and the distinct types and substitution sites of isoprenoid moieties which may possess either linear or cyclic structures. The structural diversity of PANPs endow them with various bioactivities including anti-bacterial, anti-oxidation, anti-cancer, anti-inflammatory and analgesic effects, which makes them a group of highly promising molecules for drug development. Notably, isoprenoid moieties are often the indispensable pharmacophores in these active PANPs. Aromatic prenyltransferases (aPTs) are responsible for prenylation in the biosynthesis of PANPs. aPTs can be divided into three classes according to their evolutionary relationships and structural features, i.e. membrane-bound aPTs (UbiA type), soluble aPTs with a PT barrel structure (ABBA type and DMATS type) and terpene synthase-like aPTs. Herein, we summarize 94 aPTs belonging to the different classes which were characterized in the past ten years, in particular introduce their substrate selectivity/tolerance, regioselectivity, evolutionary relationships and structural features. This would provide cues for discovery and engineering of new aPTs, and modification and bio-production of active PANPs.

     

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