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从葡萄糖作为唯一碳源生产木糖的代谢工程。

Metabolic Engineering of for Xylose Production from Glucose as the Sole Carbon Source.

机构信息

CAS Key Laboratory of Bio-Based Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China.

出版信息

ACS Synth Biol. 2021 Sep 17;10(9):2266-2275. doi: 10.1021/acssynbio.1c00184. Epub 2021 Aug 19.

DOI:10.1021/acssynbio.1c00184
PMID:34412469
Abstract

Xylose is the raw material for the synthesis of many important platform compounds. At present, xylose is commercially produced by chemical extraction. However, there are still some bottlenecks in the extraction of xylose, including complicated operation processes and the chemical substances introduced, leading to the high cost of xylose and of synthesizing the downstream compounds of xylose. The current market price of xylose is 8× that of glucose, so using low-cost glucose as the substrate to produce the downstream compounds of xylose can theoretically reduce the cost by 70%. Here, we designed a pathway for the biosynthesis of xylose from glucose in . This biosynthetic pathway was achieved by overexpressing five genes, namely, , , , , and , while replacing the native xylulose kinase gene with from , which displays phosphatase activity toward d-xylulose 5-phosphate. The yield of xylose was increased to 3.3 g/L by optimizing the metabolic pathway. Furthermore, xylitol was successfully synthesized by introducing the gene, which suggested that the biosynthetic pathway of xylose from glucose is universally applicable for the synthesis of xylose downstream compounds. This is the first study to synthesize xylose and its downstream compounds by using glucose as a substrate, which not only reduces the cost of raw materials, but also alleviates carbon catabolite repression (CCR), providing a new idea for the synthesis of downstream compounds of xylose.

摘要

木糖是许多重要平台化合物合成的原料。目前,木糖是通过化学提取商业化生产的。然而,木糖的提取仍存在一些瓶颈,包括复杂的操作过程和引入的化学物质,导致木糖的成本和木糖下游化合物的合成成本都很高。木糖的当前市场价格是葡萄糖的 8 倍,因此,以低成本的葡萄糖为底物来生产木糖的下游化合物,理论上可以降低 70%的成本。在这里,我们设计了一种在 中从葡萄糖生物合成木糖的途径。通过过表达五个基因,即 、 、 、 、和 ,同时用来自 的磷酸酶活性的木酮糖激酶基因 替代天然的 ,实现了这个生物合成途径。通过优化代谢途径,将木糖的产量提高到 3.3 g/L。此外,通过引入 基因成功合成了木糖醇,这表明从葡萄糖生物合成木糖的途径普遍适用于木糖下游化合物的合成。这是首次使用葡萄糖作为底物来合成木糖及其下游化合物的研究,不仅降低了原材料成本,而且缓解了碳分解代谢物阻遏(CCR),为木糖下游化合物的合成提供了新的思路。

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