Metabolic engineering of Saccharomyces cerevisiae for de novo biosynthesis of aesculin and cichoriin
4 affiliations
- 1School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei 071002 China
- 2Engineering Laboratory of Microbial Breeding and Preservation of Hebei Province, Hebei University, Baoding, Hebei 071002 China
- 3Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding, Hebei 071002 China
- 4Engineering Research Center of Ecological Safety and Conservation in Beijing- Tianjin-Hebei (Xiong’an New Area) of MOE, Hebei University, Baoding, 071002 China
Abstract
Background: Coumarin glycosides are plant-derived polyphenols with diverse pharmacological activities and broad applications in the pharmaceutical, food and cosmetic industries. The low catalytic activity of 4CL and C2’H/F6’H, along with the poor stability of acyl-CoA and hydroxylated acyl-CoA intermediates, constitutes the major bottleneck for the conversion of phenolic acids to simple coumarins and limits yield improvement. Therefore, screening high-efficiency enzyme variants is critical for enhancing coumarin biosynthesis.
Results: In this study, we obtained the optimal combination Ptr4CL5‑AcF6’H1‑AtCOSY by screening esculetin synthases, which markedly enhanced the conversion efficiency of caffeic acid to esculetin, and we constructed a de novo biosynthetic pathway for esculetin. Multi-copy integration strengthened pathway flux and increased esculetin production by 87.67%. Heterologous expression of AcUGT92G7 and TOGT enabled the de novo biosynthesis of aesculin and cichoriin. Fine-tuning at the transcriptional and translational levels further optimized their titers, which reached 12.63 ± 0.31 mg/L and 8.51 ± 0.32 mg/L for aesculin and cichoriin, respectively. Meanwhile, pilot‑scale tests verified the feasibility of this strategy.
Conclusions: This study established de novo biosynthetic pathways for the two coumarin glycosides in S. cerevisiae, providing reliable strategies for efficient green biomanufacturing of coumarins and glycoside derivatives.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13036-026-00774-2.
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BibTeX
@article{pan2026metabolic,
title = {{Metabolic engineering of Saccharomyces cerevisiae for de novo biosynthesis of aesculin and cichoriin}},
author = {Shuai Pan and Boji Zhang and Qiming Wang},
journal = {Journal of Biological Engineering},
year = {2026},
month = oct,
doi = {10.1186/s13036-026-00774-2},
url = {https://doi.org/10.1186/s13036-026-00774-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Metabolic engineering of Saccharomyces cerevisiae for de novo biosynthesis of aesculin and cichoriin
AU - Shuai Pan
AU - Boji Zhang
AU - Qiming Wang
PY - 2026
DA - 2026/10/05
JO - Journal of Biological Engineering
DO - 10.1186/s13036-026-00774-2
UR - https://doi.org/10.1186/s13036-026-00774-2
AB - Background: Coumarin glycosides are plant-derived polyphenols with diverse pharmacological activities and broad applications in the pharmaceutical, food and cosmetic industries. The low catalytic activity of 4CL and C2’H/F6’H, along with the poor stability of acyl-CoA and hydroxylated acyl-CoA intermediates, constitutes the major bottleneck for the conversion of phenolic acids to simple coumarins and limits yield improvement. Therefore, screening high-efficiency enzyme variants is critical for enhancing coumarin biosynthesis. Results: In this study, we obtained the optimal combination Ptr4CL5‑AcF6’H1‑AtCOSY by screening esculetin synthases, which markedly enhanced the conversion efficiency of caffeic acid to esculetin, and we constructed a de novo biosynthetic pathway for esculetin. Multi-copy integration strengthened pathway flux and increased esculetin production by 87.67%. Heterologous expression of AcUGT92G7 and TOGT enabled the de novo biosynthesis of aesculin and cichoriin. Fine-tuning at the transcriptional and translational levels further optimized their titers, which reached 12.63 ± 0.31 mg/L and 8.51 ± 0.32 mg/L for aesculin and cichoriin, respectively. Meanwhile, pilot‑scale tests verified the feasibility of this strategy. Conclusions: This study established de novo biosynthetic pathways for the two coumarin glycosides in S. cerevisiae, providing reliable strategies for efficient green biomanufacturing of coumarins and glycoside derivatives. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13036-026-00774-2.
SN - 1754-1611
ER -