RT Journal Article SR Electronic T1 A multi-phase multi-objective genome-scale model shows diverse redox balance strategies in yeasts JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.11.430755 DO 10.1101/2021.02.11.430755 A1 David Henriques A1 Romain Minebois A1 Sebastian Mendoza A1 Laura G. Macías A1 Roberto Pérez-Torrado A1 Eladio Barrio A1 Bas Teusink A1 Amparo Querol A1 Eva Balsa-Canto YR 2021 UL http://biorxiv.org/content/early/2021/02/16/2021.02.11.430755.abstract AB Yeasts constitute over 1500 species with great potential for biotechnology. Still, the yeast Saccharomyces cerevisiae dominates industrial applications and many alternative physiological capabilities of lesser-known yeasts are not being fully exploited. While comparative genomics receives substantial attention, little is known about yeasts’ metabolic specificity in batch cultures. Here we propose a multi-phase multi-objective dynamic genome-scale model of yeast batch cultures that describes the uptake of carbon and nitrogen sources and the production of primary and secondary metabolites. The model integrates a specific metabolic reconstruction, based on the consensus Yeast8, and a kinetic model describing the time-varying culture environment. Besides, we proposed a multi-phase multi-objective flux balance analysis to compute the dynamics of intracellular fluxes. We then compared the metabolism of S. cerevisiae and S. uvarum strains in wine fermentation. The model successfully explained the experimental data and brought novel insights into how cryotolerant strains achieve redox balance. The proposed modeling captures the dynamics of metabolism throughout the batch and offers a systematic approach to prospect or engineer novel yeast cell factories.