Tuesday, 6 September 2016

Aspergillus fumigatus - a target for the discovery of novel drugs

The fungus Aspergillus fumigatus produces a group of previously unknown natural products. With reference to plant isoquinoline alkaloids, these substances have been named fumisoquins. Researchers have now discovered the novel substances while studying the fungal genome. This study shows that fungi and plants developed biosynthetic pathways for these complex molecules independently of each other. These findings make Aspergillus an interesting target for the discovery of novel drugs and their biotechnological production.

Researchers have found out that fungi synthesize certain natural products in a very similar way to plants. The scientists, from the University of Jena, analyzed the genome of the common mold Aspergillus and discovered a small cluster of genes whose function was previously unknown. Comparing these genetic sequences with known data implied that they might be responsible for the synthesis of novel natural products.

By manipulating the genetic sequences, characterizing the resulting metabolites and using radioactive labeling experiments it was possible to elucidate the structure of the novel molecules and to unravel the detailed biosynthetic pathways. The researchers discovered a new linkage mechanism for carbon atoms which had never been seen before in fungi. The whole fumisoquin biosynthetic pathway appears to be a combination of plant biosynthetic principles and the non-ribosomal peptide synthetases commonly found in fungi.

For further details, see:

Joshua A Baccile, Joseph E Spraker, Henry H Le, Eileen Brandenburger, Christian Gomez, Jin Woo Bok, Juliane Macheleidt, Axel A Brakhage, Dirk Hoffmeister, Nancy P Keller, Frank C Schroeder. Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus fumigatus. Nature Chemical Biology, 2016; 12 (6): 419 DOI: 10.1038/nchembio.2061

Posted by Dr. Tim Sandle

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