Metabolomic and proteomic analysis of d-lactate-producing Lactobacillus delbrueckii under various fermentation conditions

  • Shaoxiong Liang
  • Dacheng Gao
  • Huanhuan Liu
  • Cheng Wang
  • Jianping WenEmail author
Fermentation, Cell Culture and Bioengineering - Original Paper


As an important feedstock monomer for the production of biodegradable stereo-complex poly-lactic acid polymer, d-lactate has attracted much attention. To improve d-lactate production by microorganisms such as Lactobacillus delbrueckii, various fermentation conditions were performed, such as the employment of anaerobic fermentation, the utilization of more suitable neutralizing agents, and exploitation of alternative nitrogen sources. The highest d-lactate titer could reach 133 g/L under the optimally combined fermentation condition, increased by 70.5% compared with the control. To decipher the potential mechanisms of d-lactate overproduction, the time-series response of intracellular metabolism to different fermentation conditions was investigated by GC–MS and LC–MS/MS-based metabolomic analysis. Then the metabolomic datasets were subjected to weighted correlation network analysis (WGCNA), and nine distinct metabolic modules and eight hub metabolites were identified to be specifically associated with d-lactate production. Moreover, a quantitative iTRAQ–LC–MS/MS proteomic approach was employed to further analyze the change of intracellular metabolism under the combined fermentation condition, identifying 97 up-regulated and 42 down-regulated proteins compared with the control. The in-depth analysis elucidated how the key factors exerted influence on d-lactate biosynthesis. The results revealed that glycolysis and pentose phosphate pathways, transport of glucose, amino acids and peptides, amino acid metabolism, peptide hydrolysis, synthesis of nucleotides and proteins, and cell division were all strengthened, while ATP consumption for exporting proton, cell damage, metabolic burden caused by stress response, and bypass of pyruvate were decreased under the combined condition. These might be the main reasons for significantly improved d-lactate production. These findings provide the first omics view of cell growth and d-lactate overproduction in L. delbrueckii, which can be a theoretical basis for further improving the production of d-lactate.


d-lactate Fermentation condition Metabolomics Proteomics Lactobacillus delbrueckii 



This work was financially supported by the National Natural Science Foundation of China (no. 21676189); and the key technologies R & D program of Tianjin (no. 16YFZCSY00780).

Supplementary material

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Supplementary material 1 (XLSX 271 kb)
10295_2018_2048_MOESM2_ESM.pdf (555 kb)
Supplementary material 2 (PDF 555 kb)


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  • Shaoxiong Liang
    • 1
    • 2
  • Dacheng Gao
    • 3
  • Huanhuan Liu
    • 4
    • 5
  • Cheng Wang
    • 1
    • 2
  • Jianping Wen
    • 1
    • 2
    Email author
  1. 1.Key Laboratory of Systems Bioengineering (Ministry of Education)Tianjin UniversityTianjinPeople’s Republic of China
  2. 2.SynBio Research PlatformCollaborative Innovation Center of Chemical Science and Engineering (Tianjin)TianjinPeople’s Republic of China
  3. 3.Dalian Research Institute of Petroleum and PetrochemicalsSINOPECDalianPeople’s Republic of China
  4. 4.State Key Laboratory of Food Nutrition and SafetyTianjin University of Science and TechnologyTianjinChina
  5. 5.Key Laboratory of Food Nutrition and Safety, Ministry of EducationTianjin University of Science and TechnologyTianjinChina

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