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利用代谢工程可持续生产香叶醇。

Metabolic Engineering of for Sustainable Production of Geraniol.

机构信息

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

出版信息

ACS Synth Biol. 2023 Jun 16;12(6):1836-1844. doi: 10.1021/acssynbio.3c00195. Epub 2023 Jun 4.

Abstract

Geraniol is a class of natural products that are widely used in the aroma industry due to their unique aroma. Here, to achieve the synthesis of geraniol and alleviate the intense competition from the yeast ergosterol pathway, a transcription factor-mediated ergosterol feedback system was developed in this study to autonomously regulate ergosterol metabolism and redirect carbon flux to geraniol synthesis. In addition, the modification of ergosterol-responsive promoters, the optimization of transcription factor expression intensity, and stepwise metabolic engineering resulted in a geraniol titer of 531.7 mg L. For sustainable production of geraniol, we constructed a xylose assimilation pathway in (). Then, the xylose metabolic capacity was ameliorated and the growth of the engineered strain was rescued by activating the pentose phosphate (PP) pathway. Finally, we obtained 1091.6, 862.4, and 921.8 mg L of geraniol in a 5 L bioreactor by using pure glucose, simulated wheat straw hydrolysates, and simulated sugarcane bagasse hydrolysates, with yields of 47.5, 57.9, and 59.1 mg g DCW, respectively. Our study demonstrated that has the potential to produce geraniol from lignocellulosic biomass, providing a powerful tool for the sustainable synthesis of other valuable monoterpenes.

摘要

香叶醇是一类天然产物,由于其独特的香气,广泛应用于香料工业。在这里,为了实现香叶醇的合成并缓解酵母麦角固醇途径的激烈竞争,本研究开发了一种转录因子介导的麦角固醇反馈系统,以自主调节麦角固醇代谢并将碳通量重新导向香叶醇合成。此外,通过修饰麦角固醇响应启动子、优化转录因子表达强度以及逐步代谢工程,使香叶醇产量达到 531.7 mg/L。为了可持续生产香叶醇,我们在 () 中构建了木糖同化途径。然后,通过激活戊糖磷酸 (PP) 途径来改善工程菌株的木糖代谢能力并挽救其生长。最后,我们在 5 L 生物反应器中分别使用纯葡萄糖、模拟小麦秸秆水解物和模拟甘蔗渣水解物获得了 1091.6、862.4 和 921.8 mg/L 的香叶醇,得率分别为 47.5、57.9 和 59.1 mg g DCW。我们的研究表明,() 具有从木质纤维素生物质生产香叶醇的潜力,为其他有价值的单萜类化合物的可持续合成提供了有力工具。

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