Cyclization diversity of meroditerpenoids from endophytic fungi of medicinal plants driven by synthetic biology strategies
10.1097/st9.0000000000000060
- Author:
Yuntao JIANG
1
;
Zonghua XIAO
1
;
Lianqiong DU
1
;
Yukai SUO
1
;
Xuping ZHANG
1
;
Weiguang WANG
1
Author Information
1. Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission, Key Laboratory of Chemistry in Ethnic Medicinal Resources, Ministry of Education, Yunnan Minzu University, Kunming, China
- Publication Type:Journal Article
- Keywords:
Paris polyphyllavar.yunnanensis;
Endophytic fungi;
Meroditerpenoids;
Terpene cyclases;
Heterologous expression;
Structural decoration
- From:
Science of Traditional Chinese Medicine
2025;3(1):81-86
- CountryChina
- Language:English
-
Abstract:
Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.
