Abstract
Baicalein-7-O-glucoside and baicalein-7-O-rhamnoside have been proven to possess many pharmacological activities and are potential candidate drug leads and herb supplements. However, their further development is largely limited due to low content in host plants. Few studies reported that both bioactive plant components are prepared through the bioconversion of baicalein that is considered as the common biosynthetic precursor of both compounds. Herein, we constructed a series of the engineered whole-cell bioconversion systems in which the deletion of competitive genes and the introduction of exogenous UDP-glucose supply pathway, glucosyltransferase, rhamnosyltransferase, and the UDP-rhamnose synthesis pathway are made. Using these engineered strains, the precursor baicalein is able to be transformed into baicalein-7-O-glucoside and baicalein-7-O-rhamnoside, with high-titer production, respectively. The further optimization of fermentation conditions led to the final production of 568.8 mg/L and 877.0 mg/L for baicalein-7-O-glucoside and baicalein-7-O-rhamnoside, respectively. To the best of our knowledge, it is the highest production in preparation of baicalein-7-O-glucoside from baicalein so far, while the preparation of baicalein-7-O-rhamnoside is the first reported via bioconversion approach. Our study provides a reference for the industrial production of high-value products baicalein-7-O-glucoside and baicalein-7-O-rhamnoside using engineered E. coli.
Key points
• Integrated design for improving the intracellular UDP-glucose pool
• High production of rare baicalein glycosides in the engineered E. coli
• Baicalein-7-O-glucoside and baicalein-7-O-rhamnoside
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Data availability
The datasets generated and/or analyzed during the current work are available from the corresponding author upon reasonable request.
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This work was supported by the National Key R & D Program of China (2022YFD2200605).
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XM and JX conceived the idea of this manuscript. XM, JX, SC, and HZ conducted all experiments. JP provided partial plasmids used in this study. All authors analyzed the data and contributed to scientific discussions. XM, JX, SB, and LZ wrote the manuscript. All authors read and approved the manuscript.
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Zhang, X., Xie, J., Cao, S. et al. Efficient production of the glycosylated derivatives of baicalein in engineered Escherichia coli. Appl Microbiol Biotechnol 107, 2831–2842 (2023). https://doi.org/10.1007/s00253-023-12464-w
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DOI: https://doi.org/10.1007/s00253-023-12464-w