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An economically and environmentally acceptable synthesis of chiral drug intermediate l-pipecolic acid from biomass-derived lysine via artificially engineered microbes

  • Metabolic Engineering and Synthetic Biology - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Deficiency in petroleum resources and increasing environmental concerns have pushed a bio-based economy to be built, employing a highly reproducible, metal contaminant free, sustainable and green biomanufacturing method. Here, a chiral drug intermediate l-pipecolic acid has been synthesized from biomass-derived lysine. This artificial bioconversion system involves the coexpression of four functional genes, which encode l-lysine α-oxidase from Scomber japonicus, glucose dehydrogenase from Bacillus subtilis, Δ1-piperideine-2-carboxylase reductase from Pseudomonas putida, and lysine permease from Escherichia coli. Besides, a lysine degradation enzyme has been knocked out to strengthen the process in this microbe. The overexpression of LysP improved the l-pipecolic acid titer about 1.6-folds compared to the control. This engineered microbial factory showed the highest l-pipecolic acid production of 46.7 g/L reported to date and a higher productivity of 2.41 g/L h and a yield of 0.89 g/g. This biotechnological l-pipecolic acid production is a simple, economic, and green technology to replace the presently used chemical synthesis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21206175 and 315014682), the Industrial Biotechnology Program of Tianjin Municipal Science and Technology Commission (14ZCZDSY00066), the Fundamental Research Funds for the Central Universities (Project No. 106112017CDJXFLX0014), and the Henan Provincial Science and technology Open cooperation projects (162106000014). This work was also partially supported by Open Funding Project of the State Key Laboratory of Bioreactor Engineering, Shanghai, China.

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  1. Key Laboratory of Chemical Process for Clean Energy and Resource Utilization, Department of Chemical Engineering, School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China

    Jie Cheng, Yuding Huang, Le Mi & Dan Wang

  2. Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People’s Republic of China

    Jie Cheng, Le Mi, Wujiu Chen & Qinhong Wang

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  1. Jie Cheng
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  2. Yuding Huang
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  3. Le Mi
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  4. Wujiu Chen
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  5. Dan Wang
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  6. Qinhong Wang
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Correspondence to Dan Wang or Qinhong Wang.

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Cheng, J., Huang, Y., Mi, L. et al. An economically and environmentally acceptable synthesis of chiral drug intermediate l-pipecolic acid from biomass-derived lysine via artificially engineered microbes. J Ind Microbiol Biotechnol 45, 405–415 (2018). https://doi.org/10.1007/s10295-018-2044-2

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