The research conducted has covered three disciplines: metabolic modeling, synthetic biology, and metabolic engineering. The main achievements can be summarized as following.
Metabolic Modeling: the genome-scale model of yeast Saccharomyces cerevisiae was extended with thermostability and regulatory constraints, as well as transcriptional regulation information. A thermodynamic model of oleaginous yeast Yarrowia lipolytica has been constructed, including a manually curated thermodynamic model of lipid metabolism.
Synthesis Biology: The ESRs have developed i) standardized toolkits for efficient genome engineering of Yarrowia lipolytica, ii) designed, constructed and applied high-throughput and automated genotyping and phenotyping workflows for Saccharomyces cerevisiae, (iii) developed and applied protein-based biosensors and other ultra-high throughput methodologies for screening of cell factories and control of cellular metabolism, as well as iv) developed streamlined directed evolution workflows.
Metabolic Engineering: The ESRs have engineered novel yeast strains that can convert sugar into value-added products as fatty alcohols, lactones, and aromatics. Pathways of first and second generation leading have been constructed using either molecular genetics or evolutionary engineering that are either able to grow without vitamins supplementation to strains able to express new enzyme co-factors enabling expansion of their enzymatic catalogue. Moreover, regulatory control circuits have enabled growth-coupling of anabolic fitness-burdening product formation, thereby safe-guarding cell factories from product-declines under industry-mimicking conditions.
Dissemination: All ESRs have participated in international outreach activities such as conferences and workshops. Also, more than 10 ESRs have organized and participated in Open Science events for the general public, and all ESRs have proactively managed the PAcMEN social media accounts and webpage. Furthermore, currently a total of 29 peer-reviewed publication have already been published by PAcMEN ESRs and many more publications are currently in preparation. The updated list of publications can be found on the PAcMEN official website www.pacmen-itn.eu. All PAcMEN papers are published with open access. The results have also been presented at over 14 international conferences, e.g. Metabolic Engienering 12, 33rd International Specialised Symposium on Yeast (ISSY33), Enzyme Engineering XXIV, and others. Moreover, the project results have been disseminated to general public through nine press releases, which have been communicated through various local and international platforms.