Genome mining reveals the evolutionary origin and biosynthetic potential of basidiomycete polyketide synthases

Lackner, Gerald; Misiek, Mathias; Braesel, Jana; Hoffmeister, Dirk

doi:10.1016/j.fgb.2012.09.009

Cited by 62 publications

(39 citation statements)

References 52 publications

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“…Compared to the A. nidulans orsellinic acid synthase (anid_07909), the C. cinerea synthase lacks the SAT domain and the second copy of ACP. As observed by Lackner et al (2012), the two synthases do not cluster together in KS based phylogenetic analyses. This suggests that PKS14 from F. graminearum is a member of orsellinic acid synthases, which are polyphyletic and can have variable domain structures.…”

Section: Phylogenetic Analyses Of Pks14mentioning

confidence: 62%

Fusarium graminearum PKS14 is involved in orsellinic acid and orcinol synthesis

Jørgensen

Frandsen

Nielsen

et al. 2014

Fungal Genetics and Biology

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a b s t r a c tThe available genome sequences show that the number of secondary metabolite genes in filamentous fungi vastly exceeds the number of known products. This is also true for the global plant pathogenic fungus Fusarium graminearum, which contains 15 polyketide synthase (PKS) genes, of which only 6 have been linked to products. To help remedy this, we focused on PKS14, which has only been shown to be expressed during plant infections or when cultivated on rice or corn meal (RM) based media. To enhance the production of the resulting product we introduced a constitutive promoter in front of PKS14 and cultivated two of the resulting mutants on RM medium. This led to the production of two compounds, which were only detected in the PKS14 overexpressing mutants and not in the wild type or PKS14 deletion mutants. The two compounds were tentatively identified as orsellinic acid and orcinol by comparing spectroscopic data (mass spectroscopy and chromatography) to authentic standards. NMR analysis of putative orcinol isolated from the PKS14 overexpressing mutant supported our identification. Orcinol and orsellinic acid, not previously detected in Fusarium, have primarily been detected in lichen fungi. Orsellinic acid is hypothesized to be the PKS release product which is transformed to orcinol through decarboxylation. Phylogenetic analyses of PKSs placed PKS14 in a subclade of known OA synthases. Expression analysis by microarray of 55 experiments identified seven genes near PKS14 that were expressed in a similar manner. One of the seven genes encodes a predicted carboxylase, which could be responsible for transforming orsellinic acid to orcinol.

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Section: Phylogenetic Analyses Of Pks14mentioning

confidence: 62%

Fusarium graminearum PKS14 is involved in orsellinic acid and orcinol synthesis

Jørgensen

Frandsen

Nielsen

et al. 2014

Fungal Genetics and Biology

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“…Indeed, a brief survey of the SciFinder returns fewer than 100 PKS-or NRPS-derived compounds from Basidiomycota, although recent work highlighting PKS diversity in Basidiomycota suggests that the number of biosynthetic genes grossly exceeds the number of reported PKs from these organisms [94]. This discrepancy most likely reflects a lack in the characterization of compounds produced by these enzymes.…”

Section: Polyketide Synthases (Pks) and Nonribosomal Peptide Synthasementioning

confidence: 99%

“…For example, a study by Lackner et al [94] aimed to identify new PKSs in Basidiomycota probing the aforementioned genome resource at JGI with the KS domain of AflC of Aspergillus parasiticus and a selected group of related sequences. Thirty-five Basidiomycota genomes were queried, yielding more than 100 putative PKS genes [94], thus supporting the claim that the myriad of domain architectures presented by fungal PKSs represent an "in silico gold mine" for the discovery of new enzymes and possibly enzymes with variant domains. A similar approach has also been used with the well-conserved PCP, A, C, and TE domains of an NRPS to infer a great deal regarding the phylogeny and functional diversity of NRPSs [85] (reviewed in [84,86]).…”

Section: Polyketide Synthases (Pks) and Nonribosomal Peptide Synthasementioning

confidence: 99%

Genome Mining for Fungal Secondary Metabolic Gene Clusters

et al. 2015

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“…Based on a previously published phylogeny of fungal PKSs, [15] the polyene synthase PPS1 falls into a distinct clade, likely representing basidiomycete highly reducing (HR-)PKSs (Figure 2). This evolutionarily separated clade is unrelated to known bacterial double-bond-forming PKSs of various phylogenetic clades (e.g.…”

Section: Introductionmentioning

confidence: 99%

Induced Chemical Defense of a Mushroom by a Double‐Bond‐Shifting Polyene Synthase

et al. 2017

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The antilarval mushroom polyenes 18-methyl-19-oxoicosaoctaenoic acid and 20-methyl-21-oxodocosanonaenoic acid appear in response to injury of the mycelium of the stereaceous mushroom BY1. We identified a polyketide synthase (PPS1) which belongs to a hitherto completely uncharacterized clade of polyketide synthases. Expression of the PPS1 gene is massively upregulated following mycelial damage. The synthesis of the above polyenes was reconstituted in the mold Aspergillus niger as a heterologous host. This demonstrates that PPS1 1) synchronously produces branched-chain polyketides of varied lengths, and 2) catalyzes the unprecedented shift of eight or nine double bonds. This study represents the first characterization of a reducing polyketide synthase from a mushroom. We also show that injury-induced de novo synthesis of polyketides is a fungal response strategy.

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Genome mining reveals the evolutionary origin and biosynthetic potential of basidiomycete polyketide synthases

Cited by 62 publications

References 52 publications

Fusarium graminearum PKS14 is involved in orsellinic acid and orcinol synthesis

Fusarium graminearum PKS14 is involved in orsellinic acid and orcinol synthesis

Genome Mining for Fungal Secondary Metabolic Gene Clusters

Induced Chemical Defense of a Mushroom by a Double‐Bond‐Shifting Polyene Synthase

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