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Modulating heterologous pathways and optimizing fermentation conditions for biosynthesis of kaempferol and astragalin from naringenin in Escherichia coli

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

Abstract

Kaempferol and astragalin are used as standards to assess the quality of Ginkgo biloba extract and Radix astragali, respectively, and possess numerous biological properties. In this study, we constructed a recombinant strain with a highly efficient biosynthetic pathway of kaempferol by screening key enzyme genes, designing a synthetic fusion enzyme and increasing the gene copy number. By optimizing conversion and fed-batch fermentation conditions, maximal kaempferol production reached 1184.2 ± 16.5 mg/L, which represents the highest yield of kaempferol from naringenin reported to date. Based on this result, glycosyltransferase (AtUGT78D2) and an efficient UDP-glucose synthesis pathway were introduced into the recombinant strain to produce astragalin, resulting in maximal astragalin production at 1738.5 ± 24.8 mg/L without kaempferol accumulation. The efficient synthesis pathway described in this study for kaempferol and astragalin biosynthesis can be widely used for flavonoid biosynthesis in Escherichia coli.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2017YFD0600805), the National Natural Science Foundation of China (31570565), the Open Foundation of Jiangsu Provincial Engineering Laboratory for Biomass Conversion and Process Integration (JPELBCPI2017002), the Qing Lan Project and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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  1. Jianjun Pei, Anna Chen and Ping Dong contributed equally to this work.

Authors and Affiliations

  1. Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing, China

    Jianjun Pei, Anna Chen, Ping Dong, Xuejia Shi, Linguo Zhao & Fuliang Cao

  2. College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China

    Jianjun Pei, Anna Chen, Ping Dong, Xuejia Shi, Linguo Zhao & Fuliang Cao

  3. Jiangsu Key Lab for the Chemistry & Utilization of Agricultural and Forest Biomass, Nanjing, China

    Jianjun Pei & Linguo Zhao

  4. International Centre for Bamboo and Rattan, Beijing, China

    Feng Tang

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  1. Jianjun Pei
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Correspondence to Linguo Zhao.

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Pei, J., Chen, A., Dong, P. et al. Modulating heterologous pathways and optimizing fermentation conditions for biosynthesis of kaempferol and astragalin from naringenin in Escherichia coli. J Ind Microbiol Biotechnol 46, 171–186 (2019). https://doi.org/10.1007/s10295-018-02134-6

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