Journal of Industrial Microbiology & Biotechnology

, Volume 45, Issue 9, pp 767–780 | Cite as

Metabolomics profiling reveals the mechanism of increased pneumocandin B0 production by comparing mutant and parent strains

  • Ping Song
  • Kai Yuan
  • Tingting Qin
  • Ke Zhang
  • Xiao-jun Ji
  • Lujing Ren
  • Rongfeng Guan
  • Jianping Wen
  • He Huang
Fermentation, Cell Culture and Bioengineering - Original Paper


Metabolic profiling was used to discover mechanisms of increased pneumocandin B0 production in a high-yield strain by comparing it with its parent strain. Initially, 79 intracellular metabolites were identified, and the levels of 15 metabolites involved in six pathways were found to be directly correlated with pneumocandin B0 biosynthesis. Then by combining the analysis of key enzymes, acetyl-CoA and NADPH were identified as the main factors limiting pneumocandin B0 biosynthesis. Other metabolites, such as pyruvate, α-ketoglutaric acid, lactate, unsaturated fatty acids and previously unreported metabolite γ-aminobutyric acid were shown to play important roles in pneumocandin B0 biosynthesis and cell growth. Finally, the overall metabolic mechanism hypothesis was formulated and a rational feeding strategy was implemented that increased the pneumocandin B0 yield from 1821 to 2768 mg/L. These results provide practical and theoretical guidance for strain selection, medium optimization, and genetic engineering for pneumocandin B0 production.


Glarea lozoyensis Pneumocandin B0 Metabolomics profiling Rational feeding strategies Enzyme activity 



11-Vaccenic acid


2-Ketoglutaric acid


4-Aminobutyric acid




9,12-Octadecadienoic acid


9,12,15-Octadecatrienoic acid


9-Octadecenoic acid


Acetic acid






ATP:citrate lyase


Butanedioic acid


Chorismic acid


Citric acid


Docosanoic acid


d-Xylulose 5-phosphate




Erythrose 4-phosphate


Ethanedioic acid




Fructose 6-phosphate


Glucose 1-phosphate


Glucose 6-phosphate




Glucose-6-phosphate dehydrogenase




Gluyamic acid




Isocitrate dehydrogenase






Malic acid


Malic enzyme






Myristic acid


Nonribosomal peptide synthase


Octadecanoic acid




Oxaloacetic acid


Palmitic acid


Pentose phosphate pathway








Polyketide synthase




Pyruvate dehydrogenase


Pyruvic acid


Ribose 5-phosphate


Ribulose 5-phosphate


Sedoheptulose 7-phosphate




Shikimate metabolism


Succinic acid


Succinic semialdehyde






Tricarboxylic acid








Xylulose 5-phosphate



This work was supported by the National Science Foundation of China (No. 21776136), the National High Technology Research and Development Program (No. 2015AA021003), the Program for Innovative Research Team in University of Jiangsu Province (2015), the Natural Science Fund for Colleges and Universities in Jiangsu Province (No. 17KJB530006), the Postgraduate Research and Practice Innovation Program of Jiangsu Province (No. KYCX170960), the Natural Science Foundation of Jiangsu Province (BK20161048) and the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture (No. XTE1854). We also would like to express our sincere gratitude to the anonymous reviewers for their careful work and constructive comments that have helped improve the manuscript substantially.

Supplementary material

10295_2018_2047_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 16 kb)


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  • Ping Song
    • 1
    • 2
  • Kai Yuan
    • 2
  • Tingting Qin
    • 2
  • Ke Zhang
    • 2
  • Xiao-jun Ji
    • 2
  • Lujing Ren
    • 2
  • Rongfeng Guan
    • 3
  • Jianping Wen
    • 1
  • He Huang
    • 4
  1. 1.Department Biochemical Engineering, School Chemical Engineering and TechnologyTianjin UniversityTianjinChina
  2. 2.College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjingChina
  3. 3.Laboratory for Advanced Technology in Environmental Protection of Jiangsu ProvinceYancheng Institute of TechnologyYanchengChina
  4. 4.School of Pharmaceutical SciencesNanjing Tech UniversityNanjingChina

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