Protostadienol Biosynthesis and Metabolism in the Pathogenic Fungus <i>Aspergillus fumigatus</i>

Lodeiro, Silvia; Xiong, Quanbo; Wilson, William K.; Ivanova, Yulia; Smith, McKenzie L.; May, Gregory S.; Matsuda, Seiichi P. T.

doi:10.1021/ol802696a

Cited by 56 publications

(59 citation statements)

References 34 publications

(33 reference statements)

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“…Putative BGCs in the M. anisopliae genome were identified with the antiSMASH 3.0 [33], SMURF [34], and SMIPS [35] algorithms and previous results from the literature were also examined [31, 36, 37]. The borders of each cluster were initially detected based on the antiSMASH 3.0 prediction [33] and subsequently confirmed with CASSIS, which assumes the existence of common regulatory patterns in cluster promoters for cluster delimitation [35].…”

Section: Methodsmentioning

confidence: 99%

Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

Sbaraini

Guedes²,

Andreis

et al. 2016

BMC Genomics

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BackgroundThe described species from the Metarhizium genus are cosmopolitan fungi that infect arthropod hosts. Interestingly, while some species infect a wide range of hosts (host-generalists), other species infect only a few arthropods (host-specialists). This singular evolutionary trait permits unique comparisons to determine how pathogens and virulence determinants emerge. Among the several virulence determinants that have been described, secondary metabolites (SMs) are suggested to play essential roles during fungal infection. Despite progress in the study of pathogen-host relationships, the majority of genes related to SM production in Metarhizium spp. are uncharacterized, and little is known about their genomic organization, expression and regulation. To better understand how infection conditions may affect SM production in Metarhizium anisopliae, we have performed a deep survey and description of SM biosynthetic gene clusters (BGCs) in M. anisopliae, analyzed RNA-seq data from fungi grown on cattle-tick cuticles, evaluated the differential expression of BGCs, and assessed conservation among the Metarhizium genus. Furthermore, our analysis extended to the construction of a phylogeny for the following three BGCs: a tropolone/citrinin-related compound (MaPKS1), a pseurotin-related compound (MaNRPS-PKS2), and a putative helvolic acid (MaTERP1).ResultsAmong 73 BGCs identified in M. anisopliae, 20 % were up-regulated during initial tick cuticle infection and presumably possess virulence-related roles. These up-regulated BGCs include known clusters, such as destruxin, NG39x and ferricrocin, together with putative helvolic acid and, pseurotin and tropolone/citrinin-related compound clusters as well as uncharacterized clusters. Furthermore, several previously characterized and putative BGCs were silent or down-regulated in initial infection conditions, indicating minor participation over the course of infection.Interestingly, several up-regulated BGCs were not conserved in host-specialist species from the Metarhizium genus, indicating differences in the metabolic strategies employed by generalist and specialist species to overcome and kill their host. These differences in metabolic potential may have been partially shaped by horizontal gene transfer (HGT) events, as our phylogenetic analysis provided evidence that the putative helvolic acid cluster in Metarhizium spp. originated from an HGT event.ConclusionsSeveral unknown BGCs are described, and aspects of their organization, regulation and origin are discussed, providing further support for the impact of SM on the Metarhizium genus lifestyle and infection process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3067-6) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

Sbaraini

Guedes²,

Andreis

et al. 2016

BMC Genomics

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“…At high concentrations, fumagillin and the metabolite helvolic acid are cilioinhibitory, as mentioned previously (96). The genes required for helvolic acid synthesis have recently been identified (117), which should assist in genetically exploring the role of this metabolite in IA.…”

Section: Role Of the Neutrophilmentioning

confidence: 99%

Pathogenesis ofAspergillus fumigatusin Invasive Aspergillosis

2009

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SUMMARY Aspergillus species are globally ubiquitous saprophytes found in a variety of ecological niches. Almost 200 species of aspergilli have been identified, less than 20 of which are known to cause human disease. Among them, Aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis (IA) in the immunocompromised patient population. IA is a devastating illness, with mortality rates in some patient groups reaching as high as 90%. Studies identifying and assessing the roles of specific factors of A. fumigatus that contribute to the pathogenesis of IA have traditionally focused on single-gene deletion and mutant characterization. In combination with recent large-scale approaches analyzing global fungal responses to distinct environmental or host conditions, these studies have identified many factors that contribute to the overall pathogenic potential of A. fumigatus. Here, we provide an overview of the significant findings regarding A. fumigatus pathogenesis as it pertains to invasive disease.

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“…10). The corresponding triterpene synthase and associated fusidane biosynthetic gene cluster has been identified by two groups [222,223] (Fig. 10).…”

Section: Fungal Triterpenoid Biosynthesismentioning

confidence: 99%

Biosynthesis of Terpenoid Natural Products in Fungi

Schmidt‐Dannert

2014

Advances in Biochemical Engineering/Biotechnology

108

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Tens of thousands of terpenoid natural products have been isolated from plants and microbial sources. Higher fungi (Ascomycota and Basidiomycota) are known to produce an array of well-known terpenoid natural products, including mycotoxins, antibiotics, antitumor compounds, and phytohormones. Except for a few well-studied fungal biosynthetic pathways, the majority of genes and biosynthetic pathways responsible for the biosynthesis of a small number of these secondary metabolites have only been discovered and characterized in the past 5-10 years. This chapter provides a comprehensive overview of the current knowledge on fungal terpenoid biosynthesis from biochemical, genetic, and genomic viewpoints. Enzymes involved in synthesizing, transferring, and cyclizing the prenyl chains that form the hydrocarbon scaffolds of fungal terpenoid natural products are systematically discussed. Genomic information and functional evidence suggest differences between the terpenome of the two major fungal phyla--the Ascomycota and Basidiomycota--which will be illustrated for each group of terpenoid natural products.

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Protostadienol Biosynthesis and Metabolism in the Pathogenic Fungus Aspergillus fumigatus

Cited by 56 publications

References 34 publications

Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

Pathogenesis ofAspergillus fumigatusin Invasive Aspergillosis

Biosynthesis of Terpenoid Natural Products in Fungi

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