Genetic Characterization of Neosartorin Biosynthesis Provides Insight into Heterodimeric Natural Product Generation

A biosynthetic gene cluster of the fungal xanthone heterodimer neosartorin (1) was discovered in Aspergillus novofumigatus, and its biosynthesis was investigated by a series of gene-deletion experiments. The results indicate that the two monomeric units of 1 are synthesized by the same set of enzymes, with chrysophanol (5) as a common precursor. Furthermore, the P450 monooxygenase NsrP for the heterodimerization was discovered, which also accepts non-native substrates to afford novel xanthone dimers.