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Engineering a growth-phase-dependent biosynthetic pathway for carotenoid production in Saccharomyces cerevisiae

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

Abstract

Metabolic engineering is usually focused on static control of microbial cell factories to efficient production of interested chemicals, though heterologous pathways compete with endogenous metabolism. However, products like carotenoids may cause metabolic burden on engineering strains, thus limiting product yields and influencing strain growth. Herein, a growth-phase-dependent regulation was developed to settle this matter, and its efficiency was verified using the heterogenous biosynthesis of lycopene in Saccharomyces cerevisiae as an example. Through growth-phase-dependent control of the lycopene biosynthetic pathway, limited step in MVA pathway, and competitive squalene pathway, production yield was increased by approximately 973-fold (from 0.034- to 33.1-mg/g CDW) and 1.48 g/L of production was obtained by one-stage fermentation in a 5-L bioreactor. Our study not only introduces an economically approach to the production of carotenoids, but also provides an example of dynamic regulation of biosynthetic pathways for metabolic engineering.

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Acknowledgements

We would like to thank Guangdong Province Science and Technology Innovation Strategy Special Fund (Grant No. 2018B020206001), GDAS' Special Project of Science and Technology Development (Grant No. 2020GDASYL-20200302002), and the Science and Technology Plan Project of Guangdong Province (2016A010105013, 2019B030316017) for financial support.

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  1. State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Microbial Culture Collection Center (GDMCC), Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, People’s Republic of China

    Buli Su, Dandan Song, Fan Yang & Honghui Zhu

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  1. Buli Su
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  2. Dandan Song
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  3. Fan Yang
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  4. Honghui Zhu
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Correspondence to Honghui Zhu.

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Su, B., Song, D., Yang, F. et al. Engineering a growth-phase-dependent biosynthetic pathway for carotenoid production in Saccharomyces cerevisiae. J Ind Microbiol Biotechnol 47, 383–393 (2020). https://doi.org/10.1007/s10295-020-02271-x

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