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Applying pathway engineering to enhance production of alpha-ketoglutarate in Yarrowia lipolytica

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Abstract

α-Ketoglutarate (α-KG), one of short-chain carboxylates of high commercial relevance, has been widely used in food, medicine, chemical, and cosmetic fields. Compared to other carboxylates, α-KG occupies key positions in the tricarboxylate cycle (TCA cycle) and amino acid metabolic pathway, the over-accumulation of α-KG is restricted both by tighter carbon and nitrogen regulation process. Biotechnology production of α-KG on large industrial level has been impeded by many obstacles. This review aims at highlighting and stating recent efforts toward improving the yield and titer of α-KG in the strains of Yarrowia lipolytica to reach industrial relevance. Fermentation process optimization concerning feedstock utilization, dissolved oxygen controlling, pH manipulation and establishment of fed-batch process, have been assessed and evaluated. Moreover, pathway engineering routes have been applied for enhancing carbon commitment to α-KG, blocking competing pathways, regenerating of co-factors and regulating of carboxylate transporters to facilitate production and accumulation of α-KG. Although no engineered strain can satisfy the requirements of industrial production relevance to date, these strategies provide many clues for accelerating strain development for α-KG production.

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Authors and Affiliations

  1. Department of Biotechnology and Bioengineering, School of Chemical Engineering and Key Laboratory of Fujian Province for Biochemical Technology, National Huaqiao University, 668 Jimei Road, Amoy, Fujian, 361021, China

    Hongwei Guo, Shaojie Su, Hongwen Chen & Guo Chen

  2. UMR782, Génie et Microbiologie des Procédés Alimentaires, INRA/CNRS/AgroPan’s Tech, CBAI, BP 01, F-78850, Thiverval-Grignon, France

    Catherine Madzak

  3. School of Biotechnology and Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China

    Jingwen Zhou

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  1. Hongwei Guo
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  2. Shaojie Su
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  3. Catherine Madzak
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  4. Jingwen Zhou
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Correspondence to Hongwei Guo or Hongwen Chen.

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This work was supported by the National Natural Science Foundation of China (grant numbers: 31130043, 21276109, 21576108, 21476093), the Author of National Excellent Doctoral Dissertation of PR China (grant number: FANEDD, 201256), the Program for New Century Excellent Talents in University (grant number: NCET-12-0876), the Fundamental Research Funds for the Central Universities (grant number: JUSRP51307A), the 111 Project (grant number: 111-2-06), and the Scientific Research Funds of Huaqiao University (16BS103).

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Guo, H., Su, S., Madzak, C. et al. Applying pathway engineering to enhance production of alpha-ketoglutarate in Yarrowia lipolytica . Appl Microbiol Biotechnol 100, 9875–9884 (2016). https://doi.org/10.1007/s00253-016-7913-x

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