Molecular characterization of the PR-toxin gene cluster in Penicillium roqueforti and Penicillium chrysogenum: Cross talk of secondary metabolite pathways

Hidalgo, Pedro I.; Ullán, Ricardo V.; Albillos, Silvia M.; Montero, Olimpio; Fernández-Bodega, María Ángeles; Garcı́a-Estrada, Carlos; Fernández-Aguado, Marta; Martı́n, Juan-Francisco

doi:10.1016/j.fgb.2013.10.009

Cited by 55 publications

(74 citation statements)

References 55 publications

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“…The corresponding 1,10-cyclizing sesquiterpene synthases were cloned more than a decade ago [101,129], but only recently have studies begun to elucidate the biosynthesis of these toxins [130,131]. A gene cluster encoding the PR-toxin biosynthetic pathway has been identified in the blue cheese mold P. roqueforti by screening a genomic phage library and subsequent comparison with orthologous genes identified in the sequenced genome of a related strain, P. chysogenum [131] (Fig. 5).…”

Section: Sesquiterpenoid Biosynthetic Pathways In Ascomycota and Basimentioning

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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Section: Sesquiterpenoid Biosynthetic Pathways In Ascomycota and Basimentioning

confidence: 99%

Biosynthesis of Terpenoid Natural Products in Fungi

Schmidt‐Dannert

2014

Advances in Biochemical Engineering/Biotechnology

108

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“…The biosynthesis of different secondary metabolites by a microorganism is often coordinated (Bosello et al, 2011; Tsunematsu et al, 2013; Hidalgo et al, 2014; Vingadassalon et al, 2015; Cano-Prieto et al, 2015; Cui et al, 2016). Co-regulation of different secondary metabolites is thought to be selected during microbial evolution because it confers competitive advantages to the producing organism in microbial interactions (Challis and Hopwood, 2003).…”

Section: Introductionmentioning

confidence: 99%

Novel mechanism of metabolic co-regulation coordinates the biosynthesis of secondary metabolites in Pseudomonas protegens

Yan

Philmus

Chang

et al. 2017

eLife

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Metabolic co-regulation between biosynthetic pathways for secondary metabolites is common in microbes and can play an important role in microbial interactions. Here, we describe a novel mechanism of metabolic co-regulation in which an intermediate in one pathway is converted into signals that activate a second pathway. Our study focused on the co-regulation of 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin, two antimicrobial metabolites produced by the soil bacterium Pseudomonas protegens. We show that an intermediate in DAPG biosynthesis, phloroglucinol, is transformed by a halogenase encoded in the pyoluteorin gene cluster into mono- and di-chlorinated phloroglucinols. The chlorinated phloroglucinols function as intra- and inter-cellular signals that induce the expression of pyoluteorin biosynthetic genes, pyoluteorin production, and pyoluteorin-mediated inhibition of the plant-pathogenic bacterium Erwinia amylovora. This metabolic co-regulation provides a strategy for P. protegens to optimize the deployment of secondary metabolites with distinct roles in cooperative and competitive microbial interactions.DOI: http://dx.doi.org/10.7554/eLife.22835.001

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“…In addition to the penicillin biosynthesis gene cluster, the P. chrysogenum genome sequence [2] harbors 9 other NRPS and 15 NRPS-like, 20 PKS and 3 PKS-like, and 2 hybrid NRPS-PKS gene clusters (Figure 4). All these genes potentially encode NRPS and PKS proteins enabling the synthesis of complex secondary metabolites [3,4,38,39] (Figure 4). Co-cultivation with B. subtilis had only small effects on expression of these NRP and PK gene clusters.…”

Section: Resultsmentioning

confidence: 99%

Functional characterization of a Penicillium chrysogenum mutanase gene induced upon co-cultivation with Bacillus subtilis

et al. 2014

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BackgroundMicrobial gene expression is strongly influenced by environmental growth conditions. Comparison of gene expression under different conditions is frequently used for functional analysis and to unravel regulatory networks, however, gene expression responses to co-cultivation with other microorganisms, a common occurrence in nature, is rarely studied under laboratory conditions. To explore cellular responses of the antibiotic-producing fungus Penicillium chrysogenum to prokaryotes, the present study investigates its transcriptional responses during co-cultivation with Bacillus subtilis.ResultsSteady-state glucose-limited chemostats of P. chrysogenum grown under penillicin-non-producing conditions were inoculated with B. subtilis. Physiological and transcriptional responses of P. chrysogenum in the resulting mixed culture were monitored over 72 h. Under these conditions, B. subtilis outcompeted P. chrysogenum, as reflected by a three-fold increase of the B. subtilis population size and a two-fold reduction of the P. chrysogenum biomass concentration. Genes involved in the penicillin pathway and in synthesis of the penicillin precursors and side-chain were unresponsive to the presence of B. subtilis. Moreover, Penicillium polyketide synthase and nonribosomal peptide synthase genes were either not expressed or down-regulated. Among the highly responsive genes, two putative α-1,3 endoglucanase (mutanase) genes viz Pc12g07500 and Pc12g13330 were upregulated by more than 15-fold and 8-fold, respectively. Measurement of enzyme activity in the supernatant of mixed culture confirmed that the co-cultivation with B. subtilis induced mutanase production. Mutanase activity was neither observed in pure cultures of P. chrysogenum or B. subtilis, nor during exposure of P. chrysogenum to B. subtilis culture supernatants or heat-inactivated B. subtilis cells. However, mutanase production was observed in cultures of P. chrysogenum exposed to filter-sterilized supernatants of mixed cultures of P. chrysogenum and B. subtilis. Heterologous expression of Pc12g07500 and Pc12g13330 genes in Saccharomyces cerevisiae confirmed that Pc12g07500 encoded an active α-1,3 endoglucanase.ConclusionTime-course transcriptional profiling of P. chrysogenum revealed differentially expressed genes during co-cultivation with B. subtilis. Penicillin production was not induced under these conditions. However, induction of a newly characterized P. chrysogenum gene encoding α-1,3 endoglucanase may enhance the efficacy of fungal antibiotics by degrading bacterial exopolysaccharides.

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Molecular characterization of the PR-toxin gene cluster in Penicillium roqueforti and Penicillium chrysogenum: Cross talk of secondary metabolite pathways

Cited by 55 publications

References 55 publications

Biosynthesis of Terpenoid Natural Products in Fungi

Biosynthesis of Terpenoid Natural Products in Fungi

Novel mechanism of metabolic co-regulation coordinates the biosynthesis of secondary metabolites in Pseudomonas protegens

Functional characterization of a Penicillium chrysogenum mutanase gene induced upon co-cultivation with Bacillus subtilis

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