A systems approach on the integration of metabolic engineering and processes engineering: the case of kerosene-producing Saccharomyces cerevisiae

Ντέκας, Ιωάννης; Ntekas, Ioannis

dc.contributor.author	Ντέκας, Ιωάννης	el
dc.contributor.author	Ntekas, Ioannis	en
dc.date.accessioned	2020-05-04T19:52:53Z
dc.date.available	2020-05-04T19:52:53Z
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/50378
dc.identifier.uri	http://dx.doi.org/10.26240/heal.ntua.18076
dc.rights	Αναφορά Δημιουργού-Μη Εμπορική Χρήση 3.0 Ελλάδα	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc/3.0/gr/	*
dc.subject	Biorefinery	en
dc.subject	Βιοδιυλιστήριο	el
dc.subject	Kerosene	en
dc.subject	Genome-scale model	en
dc.subject	Superstructure	en
dc.subject	Metabolic engineering	en
dc.subject	Superstructure optimization	en
dc.subject	Κηροζίνη	el
dc.subject	Μοντέλο γονιδιακής κλίμακας	el
dc.subject	Μεταβολική μηχανική	el
dc.subject	Βελτιστοποίηση υπερδομών	el
dc.title	A systems approach on the integration of metabolic engineering and processes engineering: the case of kerosene-producing Saccharomyces cerevisiae	en
dc.title	Μια συστημική προσέγγιση για την ολοκλήρωση της μεταβολικής μηχανικής και της μηχανικής διεργασιών: Παραγωγή κηροζίνης από στέλεχος του μύκητα S.cerevisiae	el
heal.type	bachelorThesis
heal.classification	Metabolic engineering	en
heal.classification	Chemical engineering	en
heal.classification	Systems biology	en
heal.classification	Process design	en
heal.language	el
heal.language	en
heal.access	free
heal.recordProvider	ntua	el
heal.publicationDate	2019-09-30
heal.abstract	The microbial production of fuels and industrial chemicals has been identified as a promising alternative to address the depletion of fossil resources and the climate change, which is tightly correlated to anthropogenic activities. The development of efficient cell-factories requires systematic metabolic engineering of microbial strains to rewire the metabolic network towards the desired behavior. Although minimum separation costs are key determinants of a novel bioprocess viability, downstream process considerations are seldom accounted during the microbial strain design procedure. In this work, an efficient computational strain design workflow is proposed to identify metabolic interventions that succeed high product revenues while demanding minimum separation expenses. The systematic workflow comprises of five modules: In the first module, the Genome-scale Metabolic reconstruction (GEM) of a selected host organism is edited to include metabolic pathways towards a selected product portfolio and economic variables related to the upstream process and the potential product revenue. In the second module, a Mixed-Integer Linear Program (MILP) formulation is addressed to identify alternative sets of reaction eliminations that result in maximum revenue. In the third module, we sample the GEM allowed solution space that correspond to the alternative metabolic strategies and estimate the product stream composition. In the fourth module, based on the exit stream compositions we identify the optimal separation flowsheet and minimum cost for product recovery by solving the corresponding superstructure optimization problem. Finally, the average separation cost and product revenue are used to identify the most promising metabolic strategies. As a case study, we applied our workflow to rationally design a kerosene producing S.cerevisiae strain for minimum downstream separation cost. To this direction, S.cerevisiae iMM904 GEM was adapted to include hydrocarbons’ producing heterologous pathways. The developed strain design framework was applied to create a pool of alternative metabolic strategies that yield in maximum revenue. Assuming aerobic cell culture conditions in a chemostat array with glucose as the sole carbon source, the models that correspond to the distinct strategies were sampled to estimate the exit stream composition and a distillation supertask problem was solved to identify the minimum separation cost. The applied methodology identified metabolic strategies up to 7-fold more efficient with respect to the initial strain. The present formulation is the first to our knowledge that aims to bridge the strain design procedure with the downstream process synthesis, paving the way towards microbial strains tailor-made for sustainable biorefinery applications.	en
heal.advisorName	Κοκόσης, Αντώνης	el
heal.advisorName	Hatzimanikatis, Vassily	en
heal.committeeMemberName	Κοκόσης, Αντώνης	el
heal.committeeMemberName	Κέκος, Δημήτριος	el
heal.committeeMemberName	Ταραντίλη, Πετρούλα	el
heal.academicPublisher	Εθνικό Μετσόβιο Πολυτεχνείο. Σχολή Χημικών Μηχανικών. Τομέας Ανάλυσης, Σχεδιασμού και Ανάπτυξης Διεργασιών και Συστημάτων (ΙΙ)	el
heal.academicPublisherID	ntua
heal.numberOfPages	105 σ.
heal.fullTextAvailability	false