Ethanol-lactate transition of Lachancea thermotolerans is linked to nitrogen metabolism

Climate change increases sugar content in grapes, resulting in unwanted increase in ethanol content of wine. Lachancea thermotolerans ferments glucose and fructose into both ethanol and lactate, decreasing final ethanol content and positively affecting wine acidity. Reported Lachancea thermotolerans strains show big variation in lactate production during fermentation. However, a mechanistic understanding of this lactate producing phenotype is currently lacking. Through a combination of metabolomics, transcriptomics, genomics and computational methods we show that the lactate production is induced by amino acid limitation in a high lactate producing strain. We found in fermentations in synthetic grape juice media that lactate production starts in the last stages of growth, marked by decreased growth rate and increased expression levels of stress related genes. This onset of lactate production is specific for the high lactate producing strain and independent of oxygen availability. The onset of lactate production was changed by increased amino acid content of the media, and it is shown by both computational methods and amino acid measurements that at the onset of lactate production amino acids become limiting for growth. This study shows that lactate production of Lachancea thermotolerans is directly linked to nitrogen availability in the media, an insight that can further aid in the improvement of wine quality. [Display omitted] Two new strains of L. thermotolerans, a promising species for lower alcohol wine fermentation, were sequenced: one high and one low lactate producing strainA multi-omics comparison of the two L. thermotolerans strains in synthetic grape juice media link genomic differences, environmental parameters and lactate formationReduced oxygen availability increased ethanol formation in both strains, but did only increase lactate production in the high lactate producing strainA first genome-scale metabolic model of L. thermotolerans was generated and identified nitrogen as growth-limiting factor in synthetic grape juice mediaAmino acid limitation induced lactate production for high lactate producing L. thermotolerans strain