Abstract
The 6,6-quinolone scaffolds on which viridicatin-type fungal alkaloids are built are frequently found in metabolites that display useful biological activities. Here we report in vitro and computational analyses leading to the discovery of a hemocyanin-like protein AsqI from the Aspergillus nidulans aspoquinolone biosynthetic pathway that forms viridicatins via a conversion of the cyclopenin-type 6,7-bicyclic system into the viridicatin-type 6,6-bicyclic core through elimination of carbon dioxide and methylamine through methyl isocyanate.
Highlights
The 6,6-quinolone scaffolds on which viridicatin-type fungal alkaloids are built are frequently found in metabolites that display useful biological activities
The quinolone motif found commonly among such alkaloids is used as a versatile scaffold for preparing libraries of bioactive compounds2. 4′-methoxyviridicatin 3 (Fig. 1a), described in our previous report[3], and related viridicatin 6 (Fig. 1b) produced by various Penicillium sp.[4,5] carry a structurally and medicinally interesting viridicatin scaffold[6] that is found in other quinolone and quinolinone alkaloids[7,8,9,10,11]
Our previous investigation of the aspoquinolone/penigequinolone biosynthetic pathways (Fig. 1a, aspoquinolone and penigequinolone) has revealed a number of unique mechanisms involved in the formation of the family of natural products, including a highly unconventional dehydrogenation-mediated elongation of a prenyl chain[12] and subsequent cationic epoxide rearrangements of the hydroxylated prenyl chain[13] that generate structurally diverse side chain groups onto the viridicatin scaffold of 3
Summary
The 6,6-quinolone scaffolds on which viridicatin-type fungal alkaloids are built are frequently found in metabolites that display useful biological activities. When AsqI was treated with ethylenediaminetetraacetic acid, it completely lost its cyclopenase activity (Supplementary Fig. 5). The activities of AsqI and PngL were examined further by steady-state kinetic analyses using 5 and 2 as substrates (see Supplementary Methods for PngL analysis).
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