Unraveling the Biosynthetic Gene Clusters and In Silico Insights into Meroterpenoids from the Indonesian Marine Sponge Endosymbiont Fungus Aspergillus nidulans

The Indonesian marine sponge Plakortis simplex is recognized for its natural products (NPs), particularly those within the terpenoid class. Given the structural diversity of these NPs, we hypothesized that endosymbiotic microorganisms contribute to the chemical diversity within this marine eukaryotic system. Following a chemical analysis of P. simplex and a metagenomic study of biosynthesis gene clusters, we identified the presence of austinol (1) and its oxidation product, dehydroaustinol (2), through spectroscopic analysis. Further metagenomic analysis suggested that the biosynthesis gene clusters responsible for the production of compound 1 were derived from the symbiotic marine fungus Aspergillus nidulans. Additionally, the identification of characteristic gene clusters for Polyketide Synthase (PKS) and Terpenoid Cyclase from the Farnesyl Pyrophosphate (FPP) precursor confirmed the synthesis of compounds 1 and 2 as members of the meroterpenoid class. Our findings also revealed that specific genes catalyze the chemical reactions necessary for completing the synthesis of these final products. The processes involved, including in-silico studies, are described here.

• Publication year

  2025

• Venue

  Natural Resources for Human Health

• Publication date

  2025-11-09

• Fields of study

  Not labeled

• Identifiers
  DOI 10.53365/nrfhh/206017
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• The future of pharmaceuticals: Artificial intelligence in drug discovery and development

  2025cited by this paper
• Lipoprotein Signal Peptide as Adjuvants: Leveraging Lipobox-Driven TLR2 Activation in Modern Vaccine Design

  2025cited by this paper
• In silico prediction of ADMET parameters and in vitro evaluation of antioxidant and cytotoxic activities promoted by indole-thiosemicarbazone compounds.

  2024cited by this paper
• Homology Modeling, Molecular Dynamics Simulation, and Prediction of Bovine TLR2 Heterodimerization

  2024cited by this paper
• Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review

  2024cited by this paper
• Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools

  2024cited by this paper
• Immunomodulatory effect of ethanol-soluble oligopeptides from Atlantic cod (Gadus morhua)

  2023cited by this paper
• Austin Meroterpenoids from Mangrove-Derived Fungus Penicillium sp. MGP11 with α-Glucosidase Inhibitory Activity

  2022cited by this paper
• ADMET Prediction of synthesized Heterocyclic derivatives to treat renal cancer

  2022cited by this paper
• Phenolic and terpene compounds from Plectranthus amboinicus (Lour.) Spreng act as promising hepatic anticancer agents screened through in silico and in vitro approaches

  2022cited by this paper
• The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

  2022cited by this paper
• Austins-Type Meroterpenoids from a Mangrove-Derived Penicillium sp.

  2021cited by this paper
• Synthesis and Docking Study of 2–Aryl-4,5-diphenyl-1H-imidazole Derivatives as Lead Compounds for Antimalarial Agent

  2021cited by this paper
• Puupehenone, an Anticancer Produced by the Indonesian Marine Sponge Hyrtios sp.

  2021cited by this paper
• Thermochemical, PASS, Molecular Docking, Drug-Likeness and In Silico ADMET Prediction of Cytidine Derivatives against HIV-1 Reverse Transcriptase

  2021cited by this paper
• Prokaryotic, Fungal, and Unicellular Eukaryotic Core Communities Across Three Sympatric Marine Sponges From the Southwestern Atlantic Coast Are Dominated Largely by Deterministic Assemblage Processes

  2021cited by this paper
• In Silico Pharmacokinetics, ADMET Study and Conceptual DFT Analysis of Two Plant Cyclopeptides Isolated From Rosaceae as a Computational Peptidology Approach

  2021cited by this paper
• Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells

  2021cited by this paper
• TLR2 Agonistic Small Molecules: Detailed Structure-Activity Relationship, Applications, and Future Prospects.

  2020cited by this paper
• ff19SB: Amino-acid specific protein backbone parameters trained against quantum mechanics energy surfaces in solution.

  2019cited by this paper
• Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim.

  2019cited by this paper
• Identifying and engineering the ideal microbial terpenoid production host

  2019cited by this paper
• Furanoaustinol and 7-acetoxydehydroaustinol: new meroterpenoids from a marine-derived fungal strain Penicillium sp. SF-5497

  2018cited by this paper
• 3,6-Dihydroxyflavone: A Potent Inhibitor with Anti-Inflammatory Activity Targeting Toll-like Receptor 2

  2018cited by this paper
• The sponge holobiont in a changing ocean: from microbes to ecosystems

  2018cited by this paper
• Nonribosomal Peptide Synthesis-Principles and Prospects.

  2017cited by this paper
• Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters.

  2016cited by this paper
• Minimum Information about a Biosynthetic Gene cluster.

  2015cited by this paper
• Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis.

  2013cited by this paper
• An overview of the Amber biomolecular simulation package

  2013cited by this paper
• Structure and dynamic behavior of Toll‐like receptor 2 subfamily triggered by malarial glycosylphosphatidylinositols of Plasmodium falciparum

  2013cited by this paper
• Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans.

  2012cited by this paper
• Similar Structures but Different Roles – An Updated Perspective on TLR Structures

  2011cited by this paper
• Acquisition of prokaryotic genes by fungal genomes.

  2010cited by this paper
• Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.

  2007cited by this paper
• Genomics of the fungal kingdom: Insights into eukaryotic biology

  2005cited by this paper
• Lead- and drug-like compounds: the rule-of-five revolution.

  2004cited by this paper
• Polyketide biosynthesis: a millennium review.

  2001cited by this paper
• Origins and Evolution of Antibiotic Resistance

  1996cited by this paper

• No citing papers are available for this paper.