Characterization of Yarrowia lipolytica mutants affected in hydrophobic substrate utilization

Thevenieau, France; Dall, M. T. Le; Nthangeni, Bethuel; Mauersberger, Stephan; Marchal, Richard; Nicaud, Jean‐Marc

doi:10.1016/j.fgb.2006.09.001

Cited by 82 publications

(45 citation statements)

References 48 publications

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“…This finding may indicate that subsequent steps involved in terpenoid detoxification occur through the β-oxidation pathway; consistent with this, we confirmed that Gc is able to use terpenoids as a sole carbon source. Fungi that are able to use hydrophobic substrates, such as long-chain alkanes via the β-oxidation pathway, have been described (38), and fungi cultured in the presence of small amounts of terpenoids often generate nonspecific oxidized derivatives; however, the ability to grow on alkanes, such as antimicrobial monoterpenoids, as a sole carbon source is unusual. The gene-expression data described here provide an opportunity for exploring the genes and mechanisms involved in this process.…”

Section: Discussionmentioning

confidence: 99%

Genome and transcriptome analyses of the mountain pine beetle-fungal symbiont Grosmannia clavigera , a lodgepole pine pathogen

DiGuistini

Wang

Liao

et al. 2011

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

203

212

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In western North America, the current outbreak of the mountain pine beetle (MPB) and its microbial associates has destroyed wide areas of lodgepole pine forest, including more than 16 million hectares in British Columbia. Grosmannia clavigera ( Gc ), a critical component of the outbreak, is a symbiont of the MPB and a pathogen of pine trees. To better understand the interactions between Gc , MPB, and lodgepole pine hosts, we sequenced the ∼30-Mb Gc genome and assembled it into 18 supercontigs. We predict 8,314 protein-coding genes, and support the gene models with proteome, expressed sequence tag, and RNA-seq data. We establish that Gc is heterothallic, and report evidence for repeat-induced point mutation. We report insights, from genome and transcriptome analyses, into how Gc tolerates conifer-defense chemicals, including oleoresin terpenoids, as they colonize a host tree. RNA-seq data indicate that terpenoids induce a substantial antimicrobial stress in Gc , and suggest that the fungus may detoxify these chemicals by using them as a carbon source. Terpenoid treatment strongly activated a ∼100-kb region of the Gc genome that contains a set of genes that may be important for detoxification of these host-defense chemicals. This work is a major step toward understanding the biological interactions between the tripartite MPB/fungus/forest system.

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Section: Discussionmentioning

confidence: 99%

Genome and transcriptome analyses of the mountain pine beetle-fungal symbiont Grosmannia clavigera , a lodgepole pine pathogen

DiGuistini

Wang

Liao

et al. 2011

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

203

212

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“…This strategy can prevent the possible unintended metabolic consequences resulting from SNF1 deletion. Inactivation of FAA1 can interfere with the re-activation of released fatty acids that could serve in energy production, membrane maintenance, or triglyceride (TAG) homeostasis [49,79]. Deletion of the FAA1 and FAA4 genes in S. cerevisiae have been found to interfere with fatty acid incorporation in phospholipids or TAG, while generating a free fatty acid-producing phenotype [80].…”

Section: Discussionmentioning

confidence: 99%

Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

2017

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This proof-of-concept study establishes Yarrowia lipolytica (Y. lipolytica) as a whole cell factory for the de novo production of long chain dicarboxylic acid (LCDCA-16 and 18) using glycerol as the sole source of carbon. Modification of the fatty acid metabolism pathway enabled creating a pool of fatty acids in a β-oxidation deficient strain. We then selectively upregulated the native fatty acid ω-oxidation pathway for the enhanced terminal oxidation of the endogenous fatty acid precursors. Nitrogen-limiting conditions and leucine supplementation were employed to induce fatty acid biosynthesis in an engineered Leu -modified strain. Our genetic engineering strategy allowed a minimum production of 330 mg/L LCDCAs in shake flask. Scale up to a 1-L bioreactor increased the titer to 3.49 g/L. Our engineered yeast also produced citric acid as a major by-product at a titer of 39.2 g/L. These results provide basis for developing Y. lipolytica as a safe biorefinery platform for the sustainable production of high-value LCDCAs from non-oily feedstock.

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“…First identified as ALDP homologues, they were subsequently shown to encode two components of a heterodimeric transporter required for β-oxidation of long-chain (LC) FA (Hettema et al 1996;Shani and Valle 1996). Homologues are required for utilisation of hydrophobic substrates such as triglycerides and alkanes in the oleaginous yeast, Yarrowia lipolytica (Thevenieau et al 2007) but surprisingly, were found to be dispensable for peroxisomal LCFA import in the filamentous fungus, Podospora anserina (Boisnard et al 2009). The majority of fungi do not have obvious ABCD4 homologues.…”

Section: The Abcd Subfamily In Fungimentioning

confidence: 99%

Plant Peroxisomal ABC Transporters: Flexible and Unusual

Theodoulou

Baldwin

et al. 2014

Signaling and Communication in Plants

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ABC transporters of subfamily D mediate import of substrates for β-oxidation into peroxisomes. Whilst mammals possess three peroxisomal ABCD proteins which homodimerise to form transporters with distinct substrate specificities, Baker's yeast has a single transporter formed by heterodimerisation, which imports long-chain fatty acyl CoAs. Plants have a single-fused heterodimer transporter that exhibits broad substrate specificity, reflecting the wide range of β-oxidation substrates processed by plants. The fusion appears to have occurred early in the evolution of land plants and was followed by an early duplication event in the monocot lineage. Plant ABCD proteins function in all stages of the life cycle and their physiological roles reflect the ability to transport diverse substrates including saturated and unsaturated fatty acids and aromatic compounds such as precursors of hormones and secondary metabolites. Recent work suggests that transport of CoA substrates involves their cleavage and re-esterification within the peroxisome, thus interaction with appropriate acyl adenylate-activating enzymes potentially provides a mechanism for regulating entry of different substrates into β-oxidation. The mechanism of ABCD transporter targeting is broadly conserved across kingdoms but evidence suggests the regulation of protein turnover differs.

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Characterization of Yarrowia lipolytica mutants affected in hydrophobic substrate utilization

Cited by 82 publications

References 48 publications

Genome and transcriptome analyses of the mountain pine beetle-fungal symbiont Grosmannia clavigera , a lodgepole pine pathogen

Genome and transcriptome analyses of the mountain pine beetle-fungal symbiont Grosmannia clavigera , a lodgepole pine pathogen

Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

Plant Peroxisomal ABC Transporters: Flexible and Unusual

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