Molecular and metabolic adaptations of Lactococcus lactis at near-zero growth rates

This paper describes the molecular and metabolic adaptations of Lactococcus lactis during the transition from a growing to a near-zero growth state using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid fermentation during retentostat cultivation, which appeared to be controlled at the transcription level of the corresponding pyruvate-dissipation encoding genes. During retentostat cultivation, cells continued to consume several amino acids, but also produced specific amino acids, which may derive from the conversion of glycolytic intermediates. We identify a novel motif containing CTGTCAG, in the upstream regions of several genes related to amino acid conversion, which we propose to be the target site for CodY in Lactococcus lactis KF147. Finally, under extremely low carbon availability, carbon catabolite repression was progressively relieved and alternative catabolic functions were found to be highly expressed, which was confirmed by enhanced initial acidification rates on various sugars in cells obtained from near-zero growth cultures. The present integrated transcriptome and metabolite (amino acids and previously reported fermentation end-products) study provides molecular understanding of the adaptation of Lactococcus lactis to conditions supporting low-growth rates, and expands our earlier analysis of the quantitative physiology of this bacterium at near-zero growth rates towards gene regulation patterns involved in zero-growth adaptation.

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Bibliographic Details
Main Authors: Ercan, O., Wels, M., Smid, E.J., Kleerebezem, M.
Format: Article/Letter to editor biblioteca
Language:English
Subjects:acid bacteria, bacillus-subtilis, catabolite control, escherichia-coli, maintenance energy, quantitative physiology, saccharomyces-cerevisiae, streptococcus-lactis, sugar catabolism, transcriptome analysis,
Online Access:https://research.wur.nl/en/publications/molecular-and-metabolic-adaptations-of-lactococcus-lactis-at-near
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Summary:This paper describes the molecular and metabolic adaptations of Lactococcus lactis during the transition from a growing to a near-zero growth state using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid fermentation during retentostat cultivation, which appeared to be controlled at the transcription level of the corresponding pyruvate-dissipation encoding genes. During retentostat cultivation, cells continued to consume several amino acids, but also produced specific amino acids, which may derive from the conversion of glycolytic intermediates. We identify a novel motif containing CTGTCAG, in the upstream regions of several genes related to amino acid conversion, which we propose to be the target site for CodY in Lactococcus lactis KF147. Finally, under extremely low carbon availability, carbon catabolite repression was progressively relieved and alternative catabolic functions were found to be highly expressed, which was confirmed by enhanced initial acidification rates on various sugars in cells obtained from near-zero growth cultures. The present integrated transcriptome and metabolite (amino acids and previously reported fermentation end-products) study provides molecular understanding of the adaptation of Lactococcus lactis to conditions supporting low-growth rates, and expands our earlier analysis of the quantitative physiology of this bacterium at near-zero growth rates towards gene regulation patterns involved in zero-growth adaptation.