| Autor: |
Lan, Jiang, Guoliang, Zhu, Jianying, Han, Chengjian, Hou, Xue, Zhang, Zhixin, Wang, Weize, Yuan, Kangjie, Lv, Zhanren, Cong, Xinye, Wang, Xiangyin, Chen, Loganathan, Karthik, Huanting, Yang, Xuyuan, Wang, Gaoyi, Tan, Guang, Liu, Liya, Zhao, Xuekui, Xia, Xiangyang, Liu, Shushan, Gao, Lei, Ma, Mei, Liu, Biao, Ren, Huanqin, Dai, Ronald J, Quinn, Tom, Hsiang, Jingyu, Zhang, Lixin, Zhang, Xueting, Liu |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Applied microbiology and biotechnology. 105(13) |
| ISSN: |
1432-0614 |
| Popis: |
Fungal terpenoids catalyzed by bifunctional terpene synthases (BFTSs) possess interesting bioactive and chemical properties. In this study, an integrated approach of genome mining, heterologous expression, and in vitro enzymatic activity assay was used, and these identified a unique BFTS sub-clade critical to the formation of a 5-15 trans-fused bicyclic sesterterpene preterpestacin I (1). The 5-15 bicyclic BFTS gene clusters were highly conserved but showed relatively wide phylogenetic distribution across several species of the diverged fungal classes Dothideomycetes and Sordariomycetes. Further genomic organization analysis of these homologous biosynthetic gene clusters from this clade revealed a glycosyltransferase from the graminaceous pathogen Bipolaris sorokiniana isolate BS11134, which was absent in other 5-15 bicyclic BFTS gene clusters. Targeted isolation guided by BFTS gene deletion led to the identification of two new sesterterpenoids (4, and 6) from BS11134. Compounds 2 and 4 showed moderate effects on LPS-induced nitrous oxide production in the murine macrophage-like cell line RAW264.7 with in vitro inhibition rates of 36.6 ± 2.4% and 24.9 ± 2.1% at 10 μM, respectively. The plausible biosynthetic pathway of these identified compounds was proposed as well. This work revealed that phytopathogenic fungi can serve as important sources of active terpenoids via systematic analysis of the genomic organization of BFTS biosynthetic gene clusters, their phylogenetic distribution in fungi, and cyclization properties of their metabolic products. KEY POINTS: • Genome mining of the first BFTS BGC harboring a glycosyltransferase. • Gene-deletion guided isolation revealed three novel 5-15 bicyclic sesterterpenoids. • Biosynthetic pathway of isolated sesterterpenoids was proposed. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink