Exploring the Anti-Alzheimer’s Disease Potential of Aspergillus terreus C23-3 Through Genomic Insights, Metabolomic Analysis, and Molecular Docking

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder with a pressing need for novel therapeutics. However, current medications only offer symptomatic relief, without tackling the underlying pathology. To explore the bioactive potential of marine-derived fungi, this study focused on Aspergillus terreus C23-3, a strain isolated from the coral Pavona cactus in Xuwen County, China, which showed a richer metabolite fingerprint among the three deposited A. terreus strains. AntiSMASH analysis based on complete genome sequencing predicted 68 biosynthetic gene clusters (BGCs) with 7 BGCs synthesizing compounds reported to have anti-AD potential, including benzodiazepines, benzaldehydes, butenolides, and lovastatin. Liquid chromatography coupled with mass spectrometry (LC-MS)-based combinational metabolomic annotation verified most of the compounds predicted by BGCs with the acetylcholinesterase (AChE) inhibitor territrem B characterized from its fermentation extract. Subsequently, molecular docking showed that these compounds, especially aspulvione B1, possessed strong interactions with AD-related targets including AChE, cyclin-dependent kinase 5-p25 complex (CDK5/p25), glycogen synthase kinase-3β (GSK-3β), and monoamine oxidase-B (MAO-B). In conclusion, the genomic–metabolomic analyses and molecular docking indicated that C23-3 is a high-value source strain for anti-AD natural compounds.

• Publication year

  2025

• Venue

  Journal of Fungi

• Publication date

  2025-07-23

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3390/jof11080546PMID 40863500PMCID 12387979
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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