دورية أكاديمية
Metabolic engineering for the biosynthesis of bis-indolylquinone terrequinone A in Escherichia coli from L-tryptophan and prenol
| العنوان: | Metabolic engineering for the biosynthesis of bis-indolylquinone terrequinone A in Escherichia coli from L-tryptophan and prenol |
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| المؤلفون: | Lijuan Wang, Yongdong Deng, Rihe Peng, Jianjie Gao, Zhenjun Li, Wenhui Zhang, Jing Xu, Bo Wang, Yu Wang, Hongjuan Han, Xiaoyan Fu, Yongsheng Tian, Quanhong Yao |
| المصدر: | Biotechnology for Biofuels and Bioproducts, Vol 16, Iss 1, Pp 1-11 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biotechnology LCC:Fuel |
| مصطلحات موضوعية: | Biosynthesis, Bis-indolylquinone, Terrequinone A, Dimethylallyl diphosphate (DMAPP), L-tryptophan (L-Trp), Escherichia coli, Biotechnology, TP248.13-248.65, Fuel, TP315-360 |
| الوصف: | Abstract Background Terrequinone A is a bis-indolylquinone natural product with antitumor activity. Due to its unique asymmetric quinone core structure and multiple functional groups, biosynthesis is more efficient and environmentally friendly than traditional chemical synthesis. Currently, most bis-indolylquinones are obtained by direct extraction from fungi or by chemical synthesis. By focusing on the biosynthesis of terrequinone A, we hope to explore the way to synthesize bis-indolylquinones de novo using Escherichia coli as a cell factory. Results In this study, a terrequinone A synthesis pathway containing the tdiA–tdiE genes was constructed into Escherichia coli and activated by a phosphopantetheinyl transferase gene sfp, enabling the strain to synthesize 1.54 mg/L of terrequinone A. Subsequently, a two-step isopentenol utilization pathway was introduced to enhance the supply of endogenous dimethylallyl diphosphate (DMAPP) in E. coli, increasing the level of terrequinone A to 20.1 mg/L. By adjusting the L-tryptophan (L-Trp)/prenol ratio, the major product could be changed from ochrindole D to terrequinone A, and the content of terrequinone A reached the highest 106.3 mg/L under the optimized culture conditions. Metabolic analysis of L-Trp indicated that the conversion of large amounts of L-Trp to indole was an important factor preventing the further improvement of terrequinone A yield. Conclusions A comprehensive approach was adopted and terrequinone A was successfully synthesized from low-cost L-Trp and prenol in E. coli. This study provides a metabolic engineering strategy for the efficient synthesis of terrequinone A and other similar bis-indolylquinones with asymmetric quinone cores. In addition, this is the first report on the de novo biosyhthesis of terrequinone A in an engineered strain. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2731-3654 |
| Relation: | https://doaj.org/toc/2731-3654 |
| DOI: | 10.1186/s13068-023-02284-5 |
| URL الوصول: | https://doaj.org/article/80f33355ed1a4b3fa398559c6aadc8c0 |
| رقم الأكسشن: | edsdoj.80f33355ed1a4b3fa398559c6aadc8c0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 27313654 |
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| DOI: | 10.1186/s13068-023-02284-5 |