An overproduction of astellolides induced by genetic disruption of chromatin-remodeling factors in Aspergillus oryzae

Abstract

The filamentous fungus Aspergillus oryzae is an important industrial mold. Recent genomic analysis indicated that A. oryzae has a large number of biosynthetic genes for secondary metabolites (SMs), but many of the SMs they produce have not been identified. For better understanding of SMs production by A. oryzae, we screened a gene-disruption library of transcription factors including chromatin-remodeling factors and found two gene disruptions that show similarly altered SM production profiles. One is a homolog of Aspergillus nidulans cclA, a component of the histone 3 lysine 4 (H3K4) methyltransferase complex of proteins associated with Set1 complex, and the other, sppA, is an ortholog of Saccharomyces cerevisiae SPP1, another component of a complex of proteins associated with Set1 complex. The cclA and sppA disruptions in A. oryzae are deficient in trimethylation of H3K4. Furthermore, one of the SMs that increased in the cclA disruptant was identified as astellolide F (14-deacetyl astellolide B). These data indicate that both cclA and sppA affect production of SMs including astellolides by affecting the methylation status of H3K4 in A. oryzae.

Lack of the COMPASS Component Ccl1 Reduces H3K4 Trimethylation Levels and Affects Transcription of Secondary Metabolite Genes in Two Plant–Pathogenic Fusarium Species

“…In these genomic regions H3K4me3 and several subunits of the COMPASS complex have been shown to mediate gene silencing although the exact mechanism of this process has not been elucidated yet (Nislow et al, 1997; Miller et al, 2001; Krogan et al, 2002; Sims et al, 2003; Schneider et al, 2005; Wood et al, 2005; Venkatasubrahmanyam et al, 2007; Bok et al, 2009; Margaritis et al, 2012). Going in line with this, lack of cclA resulted in the induction of monodictyphenone/emodin and the two antiosteoporosis polyketides F9775A and F9775B in A. nidulans , increased gliotoxin production in A. fumigatus as well as induction of the sesquiterpenoid astellolides in A. oryzae (Bok et al, 2009; Palmer et al, 2013; Shinohara et al, 2016). Strikingly, both non-reducing PKS-encoding genes, mpdG (AN0150) and orsA (AN7909), involved in the biosynthesis of monodictyphenone/emodin and F9775A/F9775B, respectively, are localized in subtelomeric regions in A. nidulans (Klejnstrup et al, 2012).…”

“…Deletion of the bre2 homolog cclA in Aspergillus spp. resulted in increased expression of several SM cluster genes (Bok et al, 2009; Palmer et al, 2013; Shinohara et al, 2016). …”

KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans

“…However, the Set1 protein also displays some moonlighting activities as it recruits deacetylase activity independently from the H3K4me3 mark and subsequently promotes heterochromatin formation and transcriptional repression at distinct loci in the fission yeast genome [49]. This evidently negative role of the COMPASS was also documented for regulation of SMs production in three different Aspergillus species carrying genetically engineered COMPASS mutations [28, 50, 51]. Silencing specific SM gene clusters might be related to previously documented subtelomeric silencing functions of the COMPASS complex [41] and mechanistically similar to the recently identified heterochromatin-promoting role in fission yeast [49].…”

H3K4 trimethylation by CclA regulates pathogenicity and the production of three families of terpenoid secondary metabolites in Colletotrichum higginsianum

“…Although usually a characteristic of transcriptionally active regions, H3K4 methylation by COMPASS has also been implicated in the transcriptional silencing of genes located near chromosome telomeres in yeast and filamentous fungi (Krogan et al ., ). In three Aspergilli ( A. nidulans , A. fumigatus and A. oryzae ), the deletion of a COMPASS subunit called CclA (a homologue of S. cerevisiae Bre2) resulted in the overproduction of numerous different secondary metabolites (Bok et al ., ; Palmer et al ., ; Shinohara et al ., ). Deletion of a CclA homologue in Pestalotiopsis fici led to the discovery of pestaloficiols T to V and ficipyrone C (Wu et al ., ).…”