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Comparative metabolomics analysis of the key metabolic nodes in propionic acid synthesis in Propionibacterium acidipropionici

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Abstract

Propionic acid (PA) is an important platform chemical used in the agriculture, food, and pharmaceutical industries. The biosynthesis of PA by propionibacteria has become an attractive alternative to traditional petrochemical processes owing to the environmentally friendly features of biorefinery. In a previous study, we significantly increased PA production in Propionibacterium acidipropionici by improving acid tolerance via genome shuffling. In this study, we undertook metabolomics analysis of parental P. acidipropionici and its genome-shuffled mutant to find the key metabolic nodes influencing PA production. In total, 142 intracellular metabolites were identified, of which those produced in amounts of greater than twofold difference between the two strains were further investigated with principal components analysis. The regulatory functions of key metabolites involved in the PA biosynthetic pathway were also forecast and analyzed according to their potential impact on metabolism. The results indicated that the amounts of metabolic intermediates of glycolysis, the Wood–Werkman cycle, and amino acid metabolism differed markedly between parental P. acidipropionici and its mutants. Based on the results of comparative metabolomics analysis, exogenous addition of key metabolites (precursors and amino acids) was performed to improve PA production. Under optimized conditions, 105 mM lactate, 20 mM fumarate, and 30 mM succinate were added to the culture of P. acidipropionici CGMCC 1.2230 in a 3-L anaerobic fermenter, and the PA titer increased from 23.1 ± 12 to 35.8 ± 1.0 g/L. This study revealed the key metabolic nodes of PA synthesis in P. acidipropionici through comparative metabolomics analysis, which may be helpful for the metabolic engineering of P. acidipropionici for improved PA production.

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Acknowledgments

This work was financially supported by the 973 Program (2013CB733902), 111 Project (111-2-06), 863 Program (2011AA100905), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Conflict of interest

The authors declare that they have no conflict of interests.

Compliance with ethical requirements

This article does not contain any studies with human or animal subjects.

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Authors and Affiliations

  1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Ningzi Guan, Jianghua Li, Guocheng Du, Long Liu & Jian Chen

  2. Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Jianghua Li, Guocheng Du, Zhongping Shi, Long Liu & Jian Chen

  3. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, 30332, USA

    Hyun-dong Shin

  4. National Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China

    Jing Wu

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  1. Ningzi Guan
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Correspondence to Zhongping Shi or Long Liu.

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Guan, N., Li, J., Shin, Hd. et al. Comparative metabolomics analysis of the key metabolic nodes in propionic acid synthesis in Propionibacterium acidipropionici . Metabolomics 11, 1106–1116 (2015). https://doi.org/10.1007/s11306-014-0766-3

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