Studies on the production of fungal polyketides in Aspergillus nidulans using systems biology tools

ABSTRACT: Using genetic engineering tools available for the model organism Aspergillus nidulans, we constructed two recombinant strains; one expressing the model polyketide Penicillium griseofulvum 6-methylsalicylic acid (6-MSA) polyketide synthase gene, and one expressing the 6-MSA gene and overexpressing the native phosphoketolase (phk) for increasing the pool of polyketide precursor levels. The physiology of the recombinant strains and a reference wild type were characterized on glucose, xylose, glycerol and ethanol medium in controlled bioreactors. Glucose was found to be the preferable carbon source for 6-MSA production and 6-MSA titers up to 455 mg/L were achieved. Our findings indicate that overexpression of phk does not directly improve 6-MSA production on glucose but if the lower glycolysis is lowered, it is possible to obtain quite high conversion yields of sugar to 6-MSA. Systems biology tools were employed for in-depth analysis of the metabolic processes. Transcriptome analysis of 6-MSA producing strains on glucose and xylose in the presence and absence of phk overexpression combined with flux and physiology data enabled us to propose a model of phk/6msas interaction describing two different responses influencing 6-MSA production. Four strains on two carbon sources

ORGANISM(S): Emericella nidulans

SUBMITTER: Mikael Andersen 

PROVIDER: E-GEOD-12859 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress