Molecular genetic analysis of the orsellinic acid/F9775 genecluster of Aspergillus nidulans
- 16 December 2009
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Molecular BioSystems
- Vol. 6 (3), 587-593
- https://doi.org/10.1039/b904541d
Abstract
F-9775A and F-9775B are cathepsin K inhibitors that arise from a chromatin remodelling deletant strain of Aspergillus nidulans. A polyketide synthase gene has been determined to be responsible for their formation and for the simpler, archetypical polyketide orsellinic acid. We have discovered simple culture conditions that result in the production of the three compounds, and this facilitates analysis of the genes responsible for their synthesis. We have now analysed the F9775/orsellinic acid gene cluster using a set of targeted deletions. We find that the polyketide synthase alone is required for orsellinic acid biosynthesis and only two additional genes in the cluster are required for F9775 A and B synthesis. Our deletions also yielded the bioactive metabolites gerfelin and diorcinol.Keywords
This publication has 34 references indexed in Scilit:
- Intimate bacterial–fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulansProceedings of the National Academy of Sciences of the United States of America, 2009
- Chromatin-level regulation of biosynthetic gene clustersNature Chemical Biology, 2009
- The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase IProceedings of the National Academy of Sciences of the United States of America, 2008
- Molecular Genetic Mining of the Aspergillus Secondary Metabolome: Discovery of the Emericellamide Biosynthetic PathwayCell Chemical Biology, 2008
- Phosphopantetheinyl Transferase CfwA/NpgA Is Required for Aspergillus nidulans Secondary Metabolism and Asexual DevelopmentEukaryotic Cell, 2007
- Induced Production of Emericellamides A and B from the Marine-Derived Fungus Emericella sp. in Competing Co-cultureJournal of Natural Products, 2007
- Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88Nature Biotechnology, 2007
- Synthesis of Gerfelin and Related Analogous CompoundsBioscience, Biotechnology, and Biochemistry, 2006
- A New Azaphilone, Falconensin H, from Emericella falconensis.CHEMICAL & PHARMACEUTICAL BULLETIN, 1993
- Isolation of orsellinic acid synthaseBiochemical and Biophysical Research Communications, 1968