Abstract
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.
Footnotes
Funding information, This project has received funding from MCIU/AEI/FEDER, UE (grant references: RTI2018-093744-B-C31, RTI2018-093744-B-C32, RTI2018-093744-B-C33 and PID2019-104113RB-I00) and Xunta de Galicia (IN607B 2020/03). RM was supported by an FPI grant from the Ministerio de Economía y Competitividad, Spain (ref. BES-2016-078202). SNM acknowledges funding from CONICYT Becas Chile grant 72180373 (https://www.conicyt.cl/becasconicyt/).SNM and BT acknowledge support from YogurtDesign, EraCoBioTech grant 053.80.733