Glucose Metabolism and Use of Alternative Carbon Sources in Medically-Important Fungi

Chew, Shu Yih; Than, Leslie Thian Lung

doi:10.1016/b978-0-12-819990-9.00068-8

Cited by 10 publications

(6 citation statements)

References 115 publications

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“…Glyoxylate (Group 4), a metabolite, involved in the anabolic metabolic pathway derived from the TCA cycle occurring in plants, bacteria, protists, and fungi ( Chew and Than, 2021 ), is found in both control and metal treatments. The greater abundance of glyoxylate in the control cells confirmed that the metabolic machinery was optimal.…”

Section: Resultsmentioning

confidence: 99%

Molecular changes in phenolic compounds in Euglena gracilis cells grown under metal stress

Bernard

Guéguen

2023

Front. Plant Sci.

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Metal presence in the aquatic ecosystem has increased and diversified over the last decades due to anthropogenic sources. These contaminants cause abiotic stress on living organisms that lead to the production of oxidizing molecules. Phenolic compounds are part of the defense mechanisms countering metal toxicity. In this study, the production of phenolic compounds by Euglena gracilis under three different metal stressors (i.e. cadmium, copper, or cobalt) at sub-lethal concentration was assessed using an untargeted metabolomic approach by mass spectrometry combined with neuronal network analysis (i.e. Cytoscape). The metal stress had a greater impact on molecular diversity than on the number of phenolic compounds. The prevalence of sulfur- and nitrogen-rich phenolic compounds were found in Cd- and Cu-amended cultures. Together these results confirm the impact of metallic stress on phenolic compounds production, which could be utilized to assess the metal contamination in natural waters.

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Section: Resultsmentioning

confidence: 99%

Molecular changes in phenolic compounds in Euglena gracilis cells grown under metal stress

Bernard

Guéguen

2023

Front. Plant Sci.

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“…One potential approach involves the activation of the glyoxylate cycle. Given its absence in humans, this pathway is an attractive and promising target for antifungal development, primarily because of its exclusive non-human enzymes, isocitrate lyase, and malate synthase [ 1 ]. These enzymes become active in the dermatophyte T. rubrum when grown on keratin or when exposed to cytotoxic drugs in an infection-like scenario involving human keratinocytes [ 6 , 34 , 35 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Efficient nutrient assimilation by pathogenic fungi during infection is crucial for survival [ 1 , 2 ]. The dermatophyte Trichophyton rubrum infects and degrades keratinized tissues, such as nails and skin, by breaking down proteins into free amino acids and peptides [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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The Transcription Factor StuA Regulates the Glyoxylate Cycle in the Dermatophyte Trichophyton rubrum under Carbon Starvation

Petrucelli,

Martins-Santana,

Sanches

et al. 2023

IJMS

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Trichophyton rubrum is the primary causative agent of dermatophytosis worldwide. This fungus colonizes keratinized tissues and uses keratin as a nutritional source during infection. In T. rubrum–host interactions, sensing a hostile environment triggers the adaptation of its metabolic machinery to ensure its survival. The glyoxylate cycle has emerged as an alternative metabolic pathway when glucose availability is limited; this enables the conversion of simple carbon compounds into glucose via gluconeogenesis. In this study, we investigated the impact of stuA deletion on the response of glyoxylate cycle enzymes during fungal growth under varying culture conditions in conjunction with post-transcriptional regulation through alternative splicing of the genes encoding these enzymes. We revealed that the ΔstuA mutant downregulated the malate synthase and isocitrate lyase genes in a keratin-containing medium or when co-cultured with human keratinocytes. Alternative splicing of an isocitrate lyase gene yielded a new isoform. Enzymatic activity assays showed specific instances where isocitrate lyase and malate synthase activities were affected in the mutant strain compared to the wild type strain. Taken together, our results indicate a relevant balance in transcriptional regulation that has distinct effects on the enzymatic activities of malate synthase and isocitrate lyase.

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“…Succinic and lactic acid, two potentially gluconeogenic substrates, were also detected in relevant concentrations in the CSM supernatant prior to secondary culture (Figure 6). It has been shown that the regulation of the metabolic pathways involving gluconeogenesis in filamentous fungi can utilise these substrates when glucose is diminished in the media (Hynes et al, 2007;Chew and Than, 2021); this aids in explaining why CSM considerably increased the betaglucan production in the secondary T. versicolor cultures.…”

Section: Cho Spent Media (Csm) Supports Secondary Cultures the Csm Us...mentioning

confidence: 99%

Feeding secondary fermentations with mammalian and fungal culture waste streams increases productivity and resource efficiency

Lynch,

Cerrone,

O’Connor

et al. 2023

Preprint

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The evolution of the circular bioeconomy will require the realisation of new value from waste streams generated from all manufacturing processes. Bioprocessing of recombinant proteins and functional foods using animal and microbial fermentations are fast growing industries with increasing volumes of spent culture media waste resulting in significant resource inefficiency. Here Chinese hamster ovary cell spent media (CSM) and Trametes versicolor fungal cell spent media (FSM) were used as model waste streams to feed Escherichia coli in secondary fermentations. Expression of a recombinant fusion protein was used to measure the value of these streams as feedstuff. E. coli cultures fed with either waste stream in bioreactors produced equivalent yields of the protein as those fed with rich microbiological media. Separately CSM was tested as a replacement feed for the fungal cell fermentation producing beta and alpha glucans. This waste-fed fermentation resulted in a 2-fold higher glucan yield than when using standard corn steep liquor feed. Quantitative analysis of the spent media content with mass spectrometry and hplc methods showed significant differences in elemental composition profiles, quantities of individual amino acids and carboxylic acids and levels of carbon sources. These findings underline the versatility of E.coli in utilisation of waste media as a feedstuff and show that the range of applications of CHO cell culture media waste are not limited to feeding bacterial fermentation. Exploration of cellular bioprocesses that can efficiently use cell media waste as fermentation feed will be a valuable step towards increased resource efficiency in bioprocessing industries.

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Glucose Metabolism and Use of Alternative Carbon Sources in Medically-Important Fungi

Cited by 10 publications

References 115 publications

Molecular changes in phenolic compounds in Euglena gracilis cells grown under metal stress

Molecular changes in phenolic compounds in Euglena gracilis cells grown under metal stress

The Transcription Factor StuA Regulates the Glyoxylate Cycle in the Dermatophyte Trichophyton rubrum under Carbon Starvation

Feeding secondary fermentations with mammalian and fungal culture waste streams increases productivity and resource efficiency

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