Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression

Yiwei Hu; Xiaoyang Zhao; Yue Song; Jiahui Jiang; Ting Long; Mengjing Cong; Yuhua Miao; Yonghong Liu; Zhiyou Yang; Yiguang Zhu; Junfeng Wang

doi:10.1021/acs.jnatprod.4c00393

Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression

J Nat Prod. 2024 Apr 30. doi: 10.1021/acs.jnatprod.4c00393. Online ahead of print.

Authors

Yiwei Hu^{1

2}, Xiaoyang Zhao^{1

2}, Yue Song^{1

2}, Jiahui Jiang³, Ting Long¹, Mengjing Cong^{1

2}, Yuhua Miao¹, Yonghong Liu^{1

2

4}, Zhiyou Yang³, Yiguang Zhu^{1

2

4}, Junfeng Wang^{1

2

4}

Affiliations

¹ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
² University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
³ College of Food Science and Technology, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Ocean University, Zhanjiang 524088, China.
⁴ Sanya Institute of Marine Ecology and Engineering, Yazhou Scientific Bay, Sanya 572000, China.

PMID: 38687877
DOI: 10.1021/acs.jnatprod.4c00393

Abstract

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH₃ to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aβ treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.