Mitochondrial β‐oxidation in <i>Aspergillus nidulans</i>

Maggio-Hall, Lori A.; Keller, Nancy P.

doi:10.1111/j.1365-2958.2004.04340.x

Cited by 129 publications

(140 citation statements)

References 72 publications

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“…In addition, the growth phenotypes of the ␤-oxidation mutants were consistent with mitochondrial processing of short-chain fatty acids and peroxisomal activity with long-chain fatty acids, with final oxidization taking place in the mitochondria. Similar organelle contributions are observed in mammalian cells and A. nidulans (44,45,62,63,79). We did observe that linoleic acid (C 18:2 ) utilization required both mitochondrial and peroxisomal ␤-oxidation.…”

Section: Discussionsupporting

confidence: 62%

“…A defect in peroxisomal ␤-oxidation influences the stress response and extracellular protease activity. As indicated above, the inability of cells to catabolize fatty acids can lead to the accumulation of toxic fatty acids or their metabolites (16,26,40,44,45,48). In addition, a defect in ␤-oxidation can alter the lipid composition of the plasma membrane due to the absence of specific fatty acids and phospholipids (42).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, as described below, deletion analysis revealed that loss of HAD1 in C. neoformans caused phenotypes comparable to those from the loss of HAD1 in U. maydis. We also targeted the HAD1-encoded 3-OH-acyl-CoA dehydrogenase step in the mitochondrial ␤-oxidation pathway because loss of this enzyme caused the accumulation of inhibitory intermediates in A. nidulans (26,44,45). We reasoned that this might also reduce virulence for C. neoformans and therefore provide an additional incentive to target fungal ␤-oxidation as an antifungal strategy.…”

Section: Resultsmentioning

confidence: 99%

“…To test the possibility that defects in ␤-oxidation caused accumulation of toxic intermediates as seen in other fungi, the wildtype strain and the mutants were grown on the alternative carbon sources galactose, lactose, and acetate (16,26,40,44,45,48). No growth was observed on lactose, and galactose generally behaved like glucose as a catabolite-repressing carbon source (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, recent in silico surveys of the pathways encoded in more than 50 fungal genomes revealed that most fungi possess both mitochondrial and peroxisomal pathways (10,69). Mitochondrial ␤-oxidation has also been convincingly demonstrated in the saprophytic ascomycete Aspergillus nidulans (26,44,45).…”

Section: T He Basidiomycete Fungus Cryptococcus Neoformans Causes Menmentioning

confidence: 99%

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Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

2012

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ABSTRACTAn understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungusCryptococcus neoformansis important for developing antifungal therapies. Lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. In addition, lipids are important signaling molecules in both fungi and mammals. In this report, we demonstrate that defects in the peroxisomal and mitochondrial β-oxidation pathways influence the growth ofC. neoformanson fatty acids as well as the virulence of the fungus in a mouse inhalation model of cryptococcosis. Disease attenuation may be due to the cumulative influence of altered carbon source acquisition or processing, interference with secretion, changes in cell wall integrity, and an observed defect in capsule production for the peroxisomal mutant. Altered capsule elaboration in the context of a β-oxidation defect was unexpected but is particularly important because this trait is a major virulence factor forC. neoformans. Additionally, analysis of mutants in the peroxisomal pathway revealed a growth-promoting activity forC. neoformans, and subsequent work identified oleic acid and biotin as candidates for such factors. Overall, this study reveals that β-oxidation influences virulence inC. neoformansby multiple mechanisms that likely include contributions to carbon source acquisition and virulence factor elaboration.

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Section: Discussionsupporting

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: T He Basidiomycete Fungus Cryptococcus Neoformans Causes Menmentioning

confidence: 99%

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Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

2012

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Organic Synthesis with Lyases

2022

Enzyme‐Based Organic Synthesis

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Bioengineering triacetic acid lactone production in Yarrowia lipolytica for pogostone synthesis

Landberg

Shavarebi

et al. 2018

Biotech & Bioengineering

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Yarrowia lipolytica is an oleaginous yeast that is recognized for its ability to accumulate high levels of lipids, which can serve as precursors to biobased fuels and chemicals. Polyketides, such as triacetic acid lactone (TAL), can also serve as a precursor for diverse commodity chemicals. This study used Y. lipolytica as a host organism for the production of TAL via expression of the 2-pyrone synthase gene from Gerbera hybrida. Induction of lipid biosynthesis by nitrogen-limited growth conditions increased TAL titers. We also manipulated basal levels of TAL production using a DNA cut-and-paste transposon to mobilize and integrate multiple copies of the 2-pyrone synthase gene. Strain modifications and batch fermentation in nitrogen-limited medium yielded TAL titers of 2.6 g/L. Furthermore, we show that minimal medium allows TAL to be readily concentrated at >94% purity and converted at 96% yield to pogostone, a valuable antibiotic. Modifications of this reaction scheme yielded diverse related compounds. Thus, oleaginous organisms have the potential to be flexible microbial biofactories capable of economical synthesis of platform chemicals and the generation of industrially relevant molecules.

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Mitochondrial β‐oxidation in Aspergillus nidulans

Cited by 129 publications

References 72 publications

Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

Peroxisomal and Mitochondrial β-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans

Organic Synthesis with Lyases

Bioengineering triacetic acid lactone production in Yarrowia lipolytica for pogostone synthesis

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