The structurally interesting and biologically active molecule aspoquinolones, isolated from fungus Aspergillus nidulans by C. Hertweck and co-workers1, is representative members of quinolinone alkaloids. Aspoquinolone A and B contain quinolinoneskeleton and 3-oxabicyclo[3.1.0]hexane substructures. Identifying and understanding the biosynthetic pathway that can produce such molecules is of great interest. To identify the genes involved in the biosynthesis of aspoquinolones, expression of orf11 coding for nonribosomal peptide synthetase (NRPS) of the biosynthetic gene cluster in A. nidulans allowed us to clearly propose the function for the formation of cyclopeptin (CPP). The chemical structure of this compound was characterized with HR-ESI�MS, 1H NMR and 13C NMR to establish that metabolite was CPP. A structure of an overexpression orf10 coding for dioxygenase provided us for the formation of dehydrocyclopeptin (DCP) and cyclopenin (CPN) by feeding of CPP. To characterize the dioxygenase, we employed in vitro assays by using purified ORF10. Analysis of the reaction revealed that ORF10 can catalyze a dehydrogenation of CPP and followed by an epoxidation of DCP. We also observed a formation of viridicatin (VDT) by using CPN as a substrate. These results indicated that the dioxygenase can catalyze this bioconversion of dipeptide CPP to quinolinone VDT. (1) Scherlach, K. et al., Org. Biomol. Chem. 2006 , 4, 3517.

Biosynthetic study of aspoquinolones

247th National Meeting (2014)

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