Abstract

In the present study we examine the changes in the expression of genes of Lactococcus lactis subspecies cremoris MG1363 during growth in milk. To reveal which specific classes of genes (pathways, operons, regulons, COGs) are important, we performed a transcriptome time series experiment. Global analysis of gene expression over time showed that L. lactis adapted quickly to the environmental changes. Using upstream sequences of genes with correlated gene expression profiles, we uncovered a substantial number of putative DNA binding motifs that may be relevant for L. lactis fermentative growth in milk. All available novel and literature-derived data were integrated into network reconstruction building blocks, which were used to reconstruct and visualize the L. lactis gene regulatory network. This network enables easy mining in the chrono-transcriptomics data. A freely available website at http://milkts.molgenrug.nl gives full access to all transcriptome data, to the reconstructed network and to the individual network building blocks.

Highlights

  • Dairy lactic acid bacteria [LAB] such as Lactococcus lactis thrive in milk, a nutritionally rich medium that can efficiently support their sugar-based fermentative lifestyle

  • Reconstruction of the Gene Regulatory Network An interactive Gene Regulatory Network (GRN) was built using all data of the analyses described in this paper combined with literature data

  • Balanced growth is the only state with a defined physiological status of the bacterium, so not even theoretically can full reproducibility be attained with a milk medium

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Summary

Introduction

Dairy lactic acid bacteria [LAB] such as Lactococcus lactis thrive in milk, a nutritionally rich medium that can efficiently support their sugar-based fermentative lifestyle. The genome sequences have been used for extensive (phylogenetic) comparisons They have allowed examining genome-wide analyses by DNA microarray technology of a number of LAB species [2,3]. These studies and earlier work has led to the detailed description of many metabolic and regulatory networks in L. lactis, such as purine and pyrimidine biosynthesis [4,5,6], amino acid biosynthesis [7], peptide uptake and degradation [8], transcriptional regulators[9,10] and global transcriptional regulators such as CcpA [11] and CodY [12,13]. We performed chrono-transcriptomics of L. lactis fermentation of milk

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