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Advances in prenyltransferases research for modifying aromatic natural products
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Meng XIE1, Ying-ni PAN1, Ning LI1, *, Jia-chen ZI2, *
Acta Pharmaceutica Sinica | 2025, 60(3) : 573 - 586
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Acta Pharmaceutica Sinica | 2025, 60(3): 573-586
• Special Reports: Multi-disciplinary exploration in the current situation and future direction of the modernization of Traditional Chinese Medicine •
Advances in prenyltransferases research for modifying aromatic natural products
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Meng XIE1, Ying-ni PAN1, Ning LI1, *, Jia-chen ZI2, *
Affiliations
  • 1. Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning Province, Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
  • 2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Published: 2025-03-12 doi: 10.16438/j.0513-4870.2024-1067
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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.

prenylated aromatic natural product  /  aromatic prenyltransferase  /  substrate selectivity  /  regioselectivity  /  biosynthesis
Meng XIE, Ying-ni PAN, Ning LI, Jia-chen ZI. Advances in prenyltransferases research for modifying aromatic natural products[J]. Acta Pharmaceutica Sinica, 2025 , 60 (3) : 573 -586 . DOI: 10.16438/j.0513-4870.2024-1067
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Year 2025 volume 60 Issue 3
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doi: 10.16438/j.0513-4870.2024-1067
  • Receive Date：2024-09-10
  • Online Date：2025-11-06
  • Published：2025-03-12
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History
  • Received：2024-09-10
  • Revised：2025-02-18
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Affiliations
    1. Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning Province, Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
    2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
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小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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