title: Dynamic flux balancing elucidates NAD(P)H production as limiting response to furfural inhibition in Saccharomyces cerevisiae.
abstract: Achieving efficient and economical lignocellulose-based bioprocess requires a robust organism tolerant to furfural, a major inhibitory compound present in lignocellulosic hydrolysate. The aim of this study was to develop a model that could generate quantitative descriptions of cell metabolism for elucidating the cell's adaptive response to furfural. Such a modelling tool could provide strategies for the design of more robust cells. A dynamic flux balance (dFBA) model of Saccharomyces cerevisiae was created by coupling a kinetic fermentation model with a previously published genome-scale stoichiometric model. The dFBA model was used for studying intracellular and extracellular flux responses to furfural perturbations under steady state and dynamic conditions. The predicted effects of furfural on dynamic flux profiles agreed well with previously published experimental results. The model showed that the yeast cell adjusts its metabolism in response to furfural challenge by increasing fluxes through the pentose phosphate pathway, TCA cycle, and proline and serine biosynthesis in order to meet the high demand of NAD(P)H cofactors. The model described here can be used to aid in systematic optimization of the yeast, as well as of the fermentation process, for efficient lignocellulosic ethanol production.
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand. pornkamol.unr@biotec.or.th.
authors.forename: Unrean
authors.initials: U
authors.lastname: Pornkamol
authors.affiliation: Chalmers University of Technology, Department of Chemical and Biological Engineering, Division of Life Science - Industrial Biotechnology, Gothenburg, Sweden.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Franzen
mesh_terms: D056804:Biofuels; D019149:Bioreactors / Q000382:microbiology*; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D000431:Ethanol; D005285:Fermentation; D005662:Furaldehyde / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D009249:NADP / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D056804:Biofuels; D003470:Culture Media; D000431:Ethanol; D009249:NADP; D005662:Furaldehyde
keywords: Cellular robustness; Dynamic flux profiles; Furfural challenge; Saccharomyces cerevisiae; Second generation bioethanol