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Integrative Biology of Yeast Lipid Metabolism

B2L

Cécile Neuvéglise

Biodiversité et Biotechnologie des Levures

Leader: Jean-Marc Nicaud & Cécile Neuvéglise

logo bimlip

Jean-Marc Nicaud

RESEARCH PROJECT

Some yeasts are able to use hydrophobic substrates like alkanes, fatty acids or triglycerides as carbon sources. In specific conditions, some yeasts can also accumulate lipids in lipid body compartments in a very high proportion. The hemiascomycete yeast Yarrowia lipolytica possesses these two properties; it’s an oleagineous yeast able to use hydrophobic substrates, which makes it a model for lipid metabolism studies.

photo-boite-lip

Lipase production by Yarrowia lipolytica. Lipase secretion determined by the diameter of hydrolysis halos on solid medium contening triglycerides (tributyrin).

The BIMLip team (Biologie Intégrative du Métabolisme LIPidique microbien) has been at the forefront of genetic and metabolic ingeniering of Y. lipolytica, in order to exploit its properties for functional and evolutionary genomic, for lipid metabolism studies and for enzyme secretion and evolution.

- Functional and evolutionary genomics
The BIMLip team has a long experience in genomics and comparative genomics for 15 years thanks to its implication in several national and international projects (Saccharomyces cerevisiae and Schizosaccharomyces pombe genome sequencing projects, active member of the Génolevures consortium). The team develops comparative genomics and comparative transcriptomic approaches at intra- and inter-specific level. We started the functional and evolutionary analysis of the Yarrowia clade and of other oleagineous yeasts identified as more efficient in term of lipid accumulation. Sequencing and annotation of several of these species is undergoing in the lab. The use of the last high throughtput sequencing technology will allow us to search for markers of physiological behaviour variations to identify new genes involved in lipid metabolism and to decipher their regulatory networks. The fundamental knowledge acquired with different oleagineous yeasts will be exploited by metabolic ingeniering. In addition, the genomic and transcriptomic data generated are the bases for the deciphering of alternative splicing phenomenons in these yeasts, their inpacts on gene expression and regulation and on their functional role in the lipid metabolism regulation.

arbre

Lipase family evolution, example between Y. lipolytica et C. galli. Evidence of genes lost in each of the two yeasts and a recent duplication in Y. lipolytica.

- Study and rerouting of the lipid metabolism.
Understanding the lipid metabolism in microorganisms requires a strong fundamental knowledge in order to identify genes, regulatory pathway, substrate transport and specificity (chain length and fatty acid specificity). We undertake a systematic analysis of the lipid metabolism in the oleagineous yeast model Y. lipolytica. This work is center on the mechanisms involved in synthesis, assimilation, storage and degradation by combining global (genomics, transcriptomics, lipidomics...) and specific (genetic, biochemistry, enzymology...) approaches associated with metabolic flux studies. Our goal is to decipher the lipid metabolism mechanism in Y. lipolytica to modelize it in order to rerout it by metabolic ingeniering through lipids and lipid derivatives of high added value (biofuels, bioplastics, synthons...) from renewable ressources.

gut-pox

Fluorescent microscopy observations of lipid bodies labeled with Red Nil in a wild type Y. lipolytica strain (WT) and lipid over-accumulative strains (strains deleted for gut2 gene and pox1-6 genes).

- Enzyme secretion and evolution
Y. lipolytica is able to efficiently secrete enzymes in the culture medium. The BIMLip team has developped expression and amplification systems efficient for enzyme overproduction and evolution in that yeast.

lipase

Lipase secretion. Growth and lipase secretion by JMY184 strain overexpressing the LIP2 gene in multicopies. Secreted proteins analysis on SDS-PAGE gel revealed with coomassie blue.

FUNDINGS

European projects

-LipoYeasts
Mobilising the enzymatic potential of hydrocarbonoclastic bacteria and the oleaginous yeast Yarrowia lipolytica as a cellular production platform for lipid-derived industrial precursor materials.
https://www.inra.fr/la_science_et_vous/apprendre_experimenter/biotechnologies/lipides_d_interet_industriel
www.lipoyeasts.ugent.be/booklet%20Lipoyeasts%20jan%202010.pdf
-Alfa Bird
«ALternative Fuels And Biofuels for aIRcraft Development ».
www.alfa-bird.eu-vri.eu/

ANR

-GB-3G
Unravelling Genome Biology through a unique combination of comparative Genomics, functional
Genomics and population Genomics (3G)

-Yeastintrons
Global analysis of PTC-containing RNA regulation by the NMD pathway and the EJC-like in intron-rich and intron-poor yeasts

-OLEOVISION (FUI), Production d'huiles de tournesol de hautes spécificités pour l'Industrie

Others

-INRA, 3BCAR, bioénergies, biomolécules et biomatériaux du carbone renouvelable

-Collaborations industrielles