3.1.6. Azaphilones from *Penicillium* Genus

The *Penicillium* genus produces a great number of azaphilone metabolites [31]. *Penicillium citrinum* WK-P9 was isolated as an associated fungus from the sponge *Suberea* sp., displaying antibacterial activity. The bio-guided chemical investigation of its ethyl acetate extract led to the isolation of a new citrinin derivative called penicitrinone G (**57**) [52]. Genome mining, epigenetic regulation, optimization of culture conditions, and one-strain-many-compounds (OSMAC) were investigated as a possible way to prioritize the production of other polyketide metabolites different than the rubratoxins in *Penicillium dangeardii* [53]. Only the metabolic shunting strategy, based on the deletion of the key gene *rbtJ* encoding PKS for rubratoxins biosynthesis, and the optimization of culture conditions successfully led to the production of 35 azaphilones, from which 23 were new ones. They were identified as nine monomers named dangelones A–G (**58–64**), dangeloside A–B (**65–66**), eight dimers, didangelones A–G (**67–74**), and five trimers, tridangelones A–E (**75–79**) [53] (Figure 6). Dangelones A–G (**58–64**) have the same planar structure and the distinctions among them lay on the side chains at C-3. The differences at C-3 side chain are also present in the dimers. Still regarding *Penicillium* endophytic fungi, a strain of *Penicillium* sp. T2–11 isolated from the rhizomes of the underground portion of *Gastrodia elata* produced a citrinin dimer, named penctrimertone (**80**) [54].

**Figure 6.** Chemical structures of *Penicillium azaphilones*: **57**: penicitrinone G; **58–64**: Dangelones A–G; 65–66: dangelosides A and B; **67–74**: didangelones A–H; **75–79**: tridangelones A–E; **80**: penctrimertone [52–54].
