Biosynthesis of Steroidal Antibiotic Fusidanes: Functional Analysis of Oxidosqualene Cyclase and Subsequent Tailoring Enzymes from Aspergillus fumigatus

Mitsuguchi, Hisashi; Seshime, Yasuyo; Fujii, Isao; Shibuya, Masabumi; Ebizuka, Yutaka; Kushiro, Toshio

doi:10.1021/ja8095976

Cited by 71 publications

(68 citation statements)

References 34 publications

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“…Our genome survey indicated that the homolog of this protein is present not only in the non-specialists (e.g., MAA_03020 of M. robertsii , 82% identity) but also in M. acridum (MAC_02619, 80%) and M. album (MAM_05601, 75%). A previous study in Aspergillus fumigatus indicated that an oxidosqualene cyclase (Afu4g14770) is required for helvolic acid biosynthesis (Mitsuguchi et al, 2009). Likewise, the homolog of this cyclase is present in M. robertsii (MAA_06578, 63%), M. acridum (MAC_09947, 38%), and M. album (MAM_07210, 39%).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Conservation and Diversification of Metarhizium Species Correlate with Fungal Host-Specificity

Luo

et al. 2016

Front. Microbiol.

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The ascomycete genus Metarhizium contains several species of insect pathogenic fungi ranging from specialists with narrow host ranges to generalists that can infect diverse invertebrates. Genetic and metabolic conservations and diversifications of Metarhizium species are not well understood. In this study, using the genome information of seven Metarhizium species, we performed a comparative analysis of gene clusters involved in secondary metabolisms (SMs) in these species. The results revealed that the generalist species contain more SM gene clusters than the specialists, and that both conserved and divergent evolutions may have occurred in SM genes during fungal speciation. In particular, the loss/gain events, as well as gene mutagenesis, are evident for the gene cluster responsible for the biosynthesis of non-ribosomal cyclopeptide destruxins. The presence of conserved SM gene clusters in Metarhizium and other divergently evolved insect pathogenic fungi implies their link to fungal entomopathogenicity. Mass spectrometry based metabolomic analyses were also conducted to investigate the chemical diversities of seven Metarhizium species. Consistent with the evolutionary relationships of SM genes among the seven species, significant differences are observed in fungal metabolic profiles, whether the same or different metabolites are produced in different species. Clustering analysis based on the metabolome data revealed that Metarhizium species could be grouped based on their association to fungal host specificity. Our metabolomics-based methods also facilitate the identification of bioactive metabolites that have not been reported previously in Metarhizium. The results of this study will benefit future investigations of the chemical biology of insect-fungal interactions.

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Section: Discussionmentioning

confidence: 99%

Metabolic Conservation and Diversification of Metarhizium Species Correlate with Fungal Host-Specificity

Luo

et al. 2016

Front. Microbiol.

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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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“…A putative oxidosqualene cyclase gene with some sequence identity to fungal lanosterol synthase genes was identified in the A. fumigatus genome, as well as tailoring genes and a transporter gene that all cluster together and could plausibly contribute to helvolic acid biosynthesis. 111 The OSC gene, AfuOSC3 , was PCR amplified and expressed in yeast, the transformant bearing a known precursor to helvolic acid. Coexpression with the cluster's dehydrogenase/reductase gene or a P450 gene yielded oxidized backbone products that are in agreement with the idea the cluster is responsible for forming a tetracyclic ring system which is then tailored to helvolic acid.…”

Section: Genetic Characterization Of Other Aspergillus Secondary Mementioning

confidence: 99%

Advances in Aspergillus secondary metabolite research in the post-genomic era

et al. 2012

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This review studies the impact of whole genome sequencing on Aspergillus secondary metabolite research. There has been a proliferation of many new, intriguing discoveries since sequencing data became widely available. What is more, the genomes disclosed the surprising finding that there are many more secondary metabolite biosynthetic pathways than laboratory research had suggested. Activating these pathways has been met with some success, but many more dormant genes remain to be awakened.

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Biosynthesis of Steroidal Antibiotic Fusidanes: Functional Analysis of Oxidosqualene Cyclase and Subsequent Tailoring Enzymes from Aspergillus fumigatus

Cited by 71 publications

References 34 publications

Metabolic Conservation and Diversification of Metarhizium Species Correlate with Fungal Host-Specificity

Metabolic Conservation and Diversification of Metarhizium Species Correlate with Fungal Host-Specificity

Biosynthesis of Terpenoid Natural Products in Fungi

Advances in Aspergillus secondary metabolite research in the post-genomic era

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