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Raising the production of phloretin by alleviation of by-product of chalcone synthase in the engineered yeast

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Abstract

Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of phloretin production is still not enough for industrial application. Here, we established an artificial pathway in the yeast to produce phloretin via assembling two genes of p-coumaroyl-CoA ligase (4CL) and chalcone synthase (CHS). CHS is a key enzyme which conventionally condenses a CoA-tethered starter with three molecules of malonyl-CoA to form the backbone of flavonoids. However, there was 33% of by-product generated via CHS by condensing two molecules of malonyl-CoA during the fermentation process. Hence, we introduced a more efficient CHS and improved the supply of malonyl-CoA through two pathways; the by-product ratio was decreased from 33% to 17% and the production of phloretin was improved from 48 to 83.2 mg L−1. Finally, a fed-batch fermentation process was optimized and the production of phloretin reached 619.5 mg L−1, which was 14-fold higher than that of the previous studies. Our work established a platform for the biosynthesis of phloretin from the low-cost raw material 3-(4-hydroxyphenyl) propanoic acid and also illustrated the potential for industrial scale bio-manufacturing of phloretin.

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Acknowledgements

This work was financially supported by Talents Team Construction Fund of Northwestern Polytechnical University (NWPU) to W. W., the National Natural Science Foundation of China (31701722) and the China Postdoctoral Science Foundation (2017M620471) to C.J., the National Natural Science Foundation of China (31901026) to X.L.

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  1. Contributed equally to this work

Authors and Affiliations

  1. Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, China

    Chunmei Jiang

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

    Xiaonan Liu, Yi Cai, Yibin Zhuang, Tian Liu, Xiaoxi Zhu, Hui Wang, Yuwan Liu & Huifeng Jiang

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Xiaonan Liu & Xiaoxi Zhu

  4. Center for Ecology and Environmental Sciences, Northwestern Polytechnical University, Xi’an, 710072, China

    Xianqing Chen & Wen Wang

  5. Jiaxing Synbiolab Biotechnology Co., Ltd., Jiaxing, 314006, China

    Xianqing Chen

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  1. Chunmei Jiang
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Correspondence to Huifeng Jiang or Wen Wang.

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Jiang, C., Liu, X., Chen, X. et al. Raising the production of phloretin by alleviation of by-product of chalcone synthase in the engineered yeast. Sci. China Life Sci. 63, 1734–1743 (2020). https://doi.org/10.1007/s11427-019-1634-8

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