Regulation of secondary metabolite production in the fungal tomato pathogen Cladosporium fulvum

Griffiths, S.A.; Saccomanno, Benedetta; Wit, P.J.G.M. de; Collemare, Jérôme

doi:10.1016/j.fgb.2015.09.009

Cited by 19 publications

(27 citation statements)

References 66 publications

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“…Indeed, C. fulvum deletion mutants of the global transcriptional regulator Wor1 and the overexpression OE.CfWor1 transformant do not produce cladofulvin 1, consistent with downregulation of the PKS6 gene in both genetic backgrounds (16). Deletion of the histone deacetylase gene, CfHdaA, in C. fulvum also abolished cladofulvin production (17). Available RNA-sequencing (RNA-seq) data from the Δcfwor1 deletion mutants showed that, relative to the WT, with the exception of claA, all of the predicted cla genes are significantly down-regulated, whereas the β-tubulin control gene and clafu184401 border gene are not (Fig.…”

Section: Resultsmentioning

confidence: 72%

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Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Griffiths

Mesarich

Saccomanno

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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161

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Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps. In this study, we report the elucidation of the biosynthesis of cladofulvin, an asymmetrical homodimer of nataloe-emodin produced by the fungus Cladosporium fulvum. A gene cluster of 10 genes controls cladofulvin biosynthesis, which begins with the production of atrochrysone carboxylic acid by the polyketide synthase ClaG and the β-lactamase ClaF. This compound is decarboxylated by ClaH to yield emodin, which is then converted to chrysophanol hydroquinone by the reductase ClaC and the dehydratase ClaB. We show that the predicted cytochrome P450 ClaM catalyzes the dimerization of nataloe-emodin to cladofulvin. Remarkably, such dimerization dramatically increases nataloe-emodin cytotoxicity against mammalian cell lines. These findings shed light on the enzymatic mechanisms involved in anthraquinone dimerization. Future characterization of the ClaM enzyme should facilitate engineering the biosynthesis of novel, potent, dimeric anthraquinones and structurally related compound families.secondary metabolism | gene cluster | cytoxicity | emodin | nataloe-emodin

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Section: Resultsmentioning

confidence: 72%

“…Heterologous expression in A. oryzae and construction of C. fulvum deletion mutants were conducted as previously described (14,16,17,19). Strains were grown in standard media, and SMs were extracted using ethyl acetate.…”

Section: Methodsmentioning

confidence: 99%

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Griffiths

Mesarich

Saccomanno

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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161

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“…The alternative hypothesis is that a host‐derived signal triggers the observed down‐regulation. Previously, we have found that saccharose, the prevailing disaccharide present in the apoplast of tomato (Joosten et al ., ), specifically represses cladofulvin production (Griffiths et al ., ). Thus, in planta repression of the claG gene cluster and cladofulvin production might be triggered by C. fulvum sensing saccharose as a signal of colonizing tomato leaves.…”

Section: Discussionmentioning

confidence: 97%

“…By fusing the coding sequence of claE to the promoter region of Avr9, we aimed to induce cladofulvin biosynthesis once C. fulvum hyphae had entered the host. We first induced the expression of ClaE in vitro by growing the OE.ClaE transformant in the inductive Gamborg B5 medium without nitrogen (B5-N), which is a medium barely conducive for cladofulvin production in wild-type C. fulvum (Griffiths et al, 2015). No obvious difference between the OE.ClaE transformant and wildtype was observed under this condition.…”

Section: Induction Of the Cladofulvin Gene Cluster And Cladofulvin Prmentioning

confidence: 99%

“…The majority of C. fulvum SM gene clusters do not display evidence of inactivation, such as the accumulation of disruptive mutations (Collemare et al, 2014). Yet, only the predicted siderophore synthetase NPS9 gene and cladofulvin synthase gene claG/PKS6 are significantly expressed in C. fulvum during growth on tomato, and in different in vitro culture conditions (Collemare et al, 2014;Griffiths et al, 2015Griffiths et al, , 2016. Because claG and NPS9 are expressed in C. fulvum during the pre-penetration phase on the host leaf surface, but repressed during colonization of the apoplast surrounding tomato mesophyll cells, we hypothesized that the down-regulation and low expression levels of SM genes might be an alternative mechanism to the irreversible gene losses observed in other biotrophic pathogens (Collemare et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Down‐regulation of cladofulvin biosynthesis is required for biotrophic growth of Cladosporium fulvum on tomato

Griffiths¹,

Mesarich²,

Overdijk³

et al. 2017

Molecular Plant Pathology

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Fungal biotrophy is associated with a reduced capacity to produce potentially toxic secondary metabolites (SMs). Yet, the genome of the biotrophic plant pathogen Cladosporium fulvum contains many SM biosynthetic gene clusters, with several related to toxin production. These gene clusters are, however, poorly expressed during the colonization of tomato. The sole detectable SM produced by C. fulvum during in vitro growth is the anthraquinone cladofulvin. Although this pigment is not detected in infected leaves, cladofulvin biosynthetic genes are expressed throughout the pre-penetration phase and during conidiation at the end of the infection cycle, but are repressed during the biotrophic phase of tomato colonization. It has been suggested that the tight regulation of SM gene clusters is required for C. fulvum to behave as a biotrophic pathogen, whilst retaining potential fitness determinants for growth and survival outside its host. To address this hypothesis, we analysed the disease symptoms caused by mutant C. fulvum strains that do not produce or over-produce cladofulvin during the biotrophic growth phase. Non-producers infected tomato in a similar manner to the wild-type, suggesting that cladofulvin is not a virulence factor. In contrast, the cladofulvin over-producers caused strong necrosis and desiccation of tomato leaves, which, in turn, arrested conidiation. Consistent with the role of pigments in survival against abiotic stresses, cladofulvin protects conidia against UV light and low-temperature stress. Overall, this study demonstrates that the repression of cladofulvin production is required for C. fulvum to sustain its biotrophic lifestyle in tomato, whereas its production is important for survival outside its host.

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A Review on Biodegradable Packaging Films from Vegetative and Food Waste

Gupta¹,

Toksha

Rahaman

2022

The Chemical Record

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Plastics around the globe have been a matter of grave concern due to the unavoidable habits of human mankind. Taking waste statistics in India for the year 2019–20 into account, the data of 60 major cities show that the generation of plastic waste stands tall at around 26,000 tonnes/day, of which only about 60 % is recycled. A majority of the non‐recycled plastic waste is petrochemical‐based packaging materials that are non‐biodegradable in nature. Vegetative/food waste is another global issue, evidenced by vastly populated countries such as China and India accounting for 91 and 69 tonnes of food wastage, respectively in 2019. The mitigation of plastic packaging issues has led to key scientific developments, one of which is biodegradable materials. However, there is a way that these two waste‐related issues can be fronted as the analogy of “taking two shots with the same arrow”. The presence of various bio‐compounds such as proteins, cellulose, starch, lipids, and waxes, etc., in food and vegetative waste, creates an opportunity for the development of biodegradable packaging films. Although these flexible packaging films have limitations in terms of mechanical, permeation, and moisture absorption characteristics, they can be fine‐tuned in order to convert the biobased raw material into a realizable packaging product. These strategies could work in replacing petrochemical‐based non‐biodegradable packaging plastics which are used in enormous quantities for various household and commercial packaging applications to combat the ever‐increasing pollution in highly populated countries. This paper presents a systematic review based on modern scientific tools of the literature available with a major emphasis on the past decade and aims to serve as a standard resource for the development of biodegradable packaging films from food/vegetative waste.

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Regulation of secondary metabolite production in the fungal tomato pathogen Cladosporium fulvum

Cited by 19 publications

References 66 publications

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization

Down‐regulation of cladofulvin biosynthesis is required for biotrophic growth of Cladosporium fulvum on tomato

A Review on Biodegradable Packaging Films from Vegetative and Food Waste

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