Molecular genetic analysis of the orsellinic acid/F9775 gene cluster of Aspergillus nidulans†,‡

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Issue Date
2010-03Author
Sanchez, James F.
Chiang, Yi-Ming
Szewczyk, Edyta
Davidson, Ashley D.
Ahuja, Manmeet
Oakley, C. Elizabeth
Bok, Jin Woo
Keller, Nancy P.
Oakley, Berl R.
Wang, Clay C. C.
Publisher
Royal Society of Chemistry
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
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Show full item recordAbstract
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.
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Citation
Sanchez, J. F., Chiang, Y.-M., Szewczyk, E., Davidson, A. D., Ahuja, M., Oakley, C. E., … Wang, C. C. C. (2010). Molecular genetic analysis of the orsellinic acid/F9775 gene cluster of Aspergillus nidulans. Molecular bioSystems, 6(3), 587–593. http://doi.org/10.1039/b904541d
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