Resumen de tesis. Systems Metabolic Engineering in the industrial fungus Ashbya gossypii: boosting production of riboflavin, lipids and nucleosides

Abstract

[EN]Ashbya gossypii is a filamentous fungus used by the industry to produce riboflavin. During the last years, the natural capability of this microorganism to produce the vitamin has been increased by different metabolic engineering approaches. Since this fungus presents general industrial advantages in upstream, downstream and the fermentation processes it has been recently proposed for other large scale applications such as recombinant proteins, bioethanol and folic acid production. The objectives of this work are not only focus on the improvement of riboflavin but also in exploiting some unique capabilities of this fungus to produce novel industrial products. For this aim we developed different systems metabolic engineering approaches, we generated the first genome scale metabolic model of Ashbya, we obtained systems biology data and set up novel synthetic biology tools. We generated strains producing 5 times more riboflavin than the wild type by combinational engineering of the riboflavin and purine pathway. Additionally, we modified Ashbya to make it accumulate huge amounts of lipids. Those lipids were enriched in desired fatty acids by engineering the elongation and desaturation systems, which generates candidate strains for biodiesel production. Besides, synthetic biology allowed us to produce polyunsaturated fatty acids, omega 3 and omega 6 in A. gossypii. We also proved that the metabolism of A. gossypii can be optimized to overproduce inosine and guanosine, important industrial precursors of flavour enhancers. To sum up, this works propose A. gossypii as a promising industrial fungus for white biotechnology approaches, not only riboflavin production but also fatty acids derivatives and flavour enhancers.