Polyketides in Aspergillus terreus: biosynthesis pathway discovery and application

Area of Science:

• Biotechnology
• Mycology
• Metabolomics

Background:

• Filamentous fungi metabolites are crucial for developing new drugs.
• Aspergillus terreus is a significant producer of bioactive polyketides.
• Knowledge of biosynthesis pathways aids metabolic engineering and heterologous expression.

Purpose of the Study:

• To review polyketide biosynthesis gene clusters in Aspergillus terreus.
• To focus on polyketide synthase (PKS) genes and their metabolites.
• To explore methods for discovering and mining secondary metabolic gene clusters.

Main Methods:

• Analysis of 13 polyketide synthase (PKS) genes in the A. terreus NIH 2624 genome.
• Review of reported biosynthesis pathways for nine PKS genes.
• Homologous gene alignment to predict novel gene clusters in other Aspergillus strains.

Main Results:

• Nine PKS genes in A. terreus have known biosynthesis pathways, yielding metabolites like lovastatin, terreic acid, terrein, geodin, terretonin, citreoviridin, and asperfuranone.
• Lovastatin is a hypolipidemic agent; terreic acid, terrein, citreoviridin, and asperfuranone exhibit anticancer activities.
• Geodin and terretonin are identified as mycotoxins, highlighting the importance of gene cluster information for their control.

Conclusions:

• Biosynthesis gene cluster information is vital for targeted production or elimination of fungal metabolites.
• Predictive methods like homologous gene alignment are effective for mining new secondary metabolic gene clusters.
• Further research into A. terreus PKS genes can lead to the development of novel therapeutics and improved metabolite production strategies.