Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species

Abstract

The fungal genus of is highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse species (, ,, and )have been whole-genome PacBio sequenced to provide genetic references in three sections. and also were sequenced for SM elucidation. Thirteen genomes were analyzed with comparative genomics to determine phylogeny and genetic diversity, showing that each presented genome contains 15-27% genes not found in other sequenced Aspergilli. In particular, was compared with the pathogenic species This suggests that can produce most of the same allergens, virulence, and pathogenicity factors as, suggesting that could be as pathogenic as Furthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences, and predictive algorithms. We thus identify putative SM clusters for aflatoxin, chlorflavonin, and ochrindol in ,, and , respectively, and novofumigatonin,-cycloechinulin, and -aszonalenins in Our study delivers six fungal genomes, showing the large diversity found in the genus; highlights the potential for discovery of beneficial or harmful SMs; and supports reports of pathogenicity. It also shows how biological, biochemical, and genomic information can be combined to identify genes involved in the biosynthesis of specific SMs.

A robust phylogenomic timetree for biotechnologically and medically important fungi in the genera Aspergillus and Penicillium

“…Comparison of the topologies inferred in previous phylogenomic studies in Aspergillaceae (Yang et al 2016;Nielsen et al 2017;de Vries et al 2017;Kjaerbølling et al 2018) suggests the presence of incongruence ( Figure S1). For example, some studies have reported section Nidulantes to be the sister group to section Nigri (de Vries et al 2017), whereas other studies have placed it as the sister group to Ochraceorosei (Kjaerbølling et al 2018) ( Figure S1).…”

“…For example, it is debated whether the genus Aspergillus is monophyletic or if it includes species from other genera such as Penicillium (Pitt and Taylor 2014;Samson et al 2014). Furthermore, studies using genome-scale amounts of data, which could have the power to resolve evolutionary relationships and identify underlying causes of conflict (Rokas et al 2003;Salichos and Rokas 2013), have so far tended to use a small subset of fungi from either Aspergillus or Penicillium (Nielsen et al 2017;de Vries et al 2017;Kjaerbølling et al 2018). Additionally, these genome-scale studies do not typically examine the robustness of the produced phylogeny; rather, based on the high clade support values (e.g., bootstrap values) obtained, these studies infer that the topology obtained is highly accurate (Yang et al 2016;Nielsen et al 2017;de Vries et al 2017;Kjaerbølling et al 2018).…”

“…In recent years, several phylogenomic analyses have shown that high clade support values can be misleading (Phillips et al 2004;Kumar et al 2012;Salichos and Rokas 2013), that incongruence, the presence of topological conflict between different data sets or analyses, is widespread (Hess and Goldman 2011;Song et al 2012;Salichos and Rokas 2013;Zhong et al 2013), and that certain branches of the tree of life can be very challenging to resolve, even with genome-scale amounts of data Suh 2016;Arcila et al 2017;King and Rokas 2017;Shen et al 2017). Comparison of the topologies inferred in previous phylogenomic studies in Aspergillaceae (Yang et al 2016;Nielsen et al 2017;de Vries et al 2017;Kjaerbølling et al 2018) suggests the presence of incongruence ( Figure S1). For example, some studies have reported section Nidulantes to be the sister group to section Nigri (de Vries et al 2017), whereas other studies have placed it as the sister group to Ochraceorosei (Kjaerbølling et al 2018) ( Figure S1).…”

Functional characterization of the sterigmatocystin secondary metabolite gene cluster in the filamentous fungus Podospora anserina: involvement in oxidative stress response, sexual development, pigmentation and interspecific competitions

“…In the present work, we focused on the role of ST production in physiology of P. anserina by the functional characterization of the polyketide core gene PaStcA and the specific transcription factor PaAflR of the ST gene cluster. Genes and enzymes involved in ST metabolic pathways have been known for many years, but their molecular characterizations were mainly related to Aspergillus species, despite its discovery in several different fungal genera (Brown et al, 1996;Rank et al, 2011;Kjaerbølling et al, 2018). Previous work has established that stcA and aflR are required for the biosynthesis of ST in A. nidulans and AF in A. parasiticus and A. flavus respectively.…”

Resistance Gene-Directed Genome Mining of 50 Aspergillus species

“…This pattern and the resulting resistance mechanism 96 has previously been described in two different cases in fungi (13,16). 97 We have used complete and draft quality whole genome sequences, mainly from 98 the 300 Aspergillus sequencing project (5,6). The input for the pipeline was chosen to 99 consists of three different types of data derived from the whole genome sequence data: 100 1) predicted genes/proteins and functionally annotated proteins, for the functional 101 annotation we used InterPro (19,20).…”