Discovery of Two New Sorbicillinoids by Overexpression of the Global Regulator LaeA in a Marine-Derived Fungus Penicillium dipodomyis YJ-11

Abstract

Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) and 10,11,16,17-tetrahydrobislongiquinolide (2), as well as four known analogues, bislongiquinolide (3), 16,17-dihydrobislongiquinolide (4), sohirnone A (5), and 2′,3′-dihydrosorbicillin (6). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds.

Regulation of Secondary Metabolism in the Penicillium Genus

“…Yu et al [ 150 ] showed that the overexpression of LaeA in the Penicillium dipodomyis marine-derived strain YJ-11 leads not only to morphological but also metabolic changes. Overexpression mutants displayed the ability to produce several sorbicillinoids, two of which are new compounds, as well as four known sorbicillin analogues.…”

Heteroexpression of Aspergillus nidulans laeA in Marine-Derived Fungi Triggers Upregulation of Secondary Metabolite Biosynthetic Genes

“…by Bok and Keller has revolutionized the understanding of fungal secondary metabolism [ 11 ]. The dynamic roles of LaeA have been studied in many aspects of fungal biology, such as in asexual and sexual differentiation, in phenotype changes including pigmentation and sporulation [ 12 , 13 ], reducing [ 14 ] or increasing secondary metabolite production [ 11 , 15 , 16 ], and activation of cryptic gene clusters [ 13 , 17 ]. Numerous studies based on model Aspergillus nidulans LaeA have been carried out during the past several years, which proved its mechanisms ( Figure 1 ) and regulatory role in secondary metabolism [ 11 , 18 , 19 , 20 ].…”

Sorbicillinoid Derivatives From Sponge-Derived Fungus Trichoderma reesei (HN-2016-018)

“…In summary, we report here nine sorbicillinoid derivatives (1-9), including six new compounds, isolated from the spongederived fungus T. reesei (HN-2016-018). To date, more than 130 sorbicillinoid derivatives have been reported (Meng et al, 2016(Meng et al, , 2018(Meng et al, , 2019Zhang et al, 2018Zhang et al, , 2019Cao et al, 2019;Wang et al, 2019;Yu et al, 2019). In this study, we discovered two novel sorbicillinoids (1-2) with a characteristic naphthalenetrione ring and two rare sorbicillinoids (3-4) possessing a bicycle (3.2.1) lactone skeleton (Figure 6), where only three compounds with such distinctive skeleton have been reported previously.…”