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基于 10-DAB 提取和可再生针原位全细胞生物转化生产巴卡丁 III 的综合策略。

An Integrated Strategy Based on 10-DAB Extraction and In Situ Whole-Cell Biotransformation of Renewable Needles to Produce Baccatin III.

机构信息

School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, China.

出版信息

Molecules. 2024 May 31;29(11):2586. doi: 10.3390/molecules29112586.

Abstract

Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant strain were clarified using 10-DAB as substrate. needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of needles.

摘要

巴卡丁 III 是紫杉醇生物合成途径中的关键前体。其主要来源是从 中提取或以 10-去乙酰基巴卡丁 III(10-DAB)为底物进行化学合成。然而,这些制备方法存在严重的局限性,包括 中巴卡丁 III 的含量低和化学合成步骤复杂。在微生物菌株中异源表达 10-去乙酰基巴卡丁 III-10-O-乙酰基转移酶(TcDBAT),用于 10-DAB 的生物转化,是生产巴卡丁 III 的一种很有前途的替代策略。在这里,以 10-DAB 为底物,澄清了甘油供应和低温下略酸性条件对重组 菌株催化作用的促进作用。由于 针可再生且 10-DAB 的含量相对较高,因此可以用作催化底物 10-DAB 的有效来源。本研究通过整合从可再生 针中提取 10-DAB 和原位全细胞催化作用来合成巴卡丁 III。通过优化和建立全细胞催化生物工艺,将 40 g/L 的 针转化为 20.66 mg/L 的巴卡丁 III。本研究中使用的方法可以缩短巴卡丁 III 合成的提取生产过程,为重组菌株高效生产巴卡丁 III 和提高 针资源利用率提供可靠策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d61/11173793/e84b48c2f7eb/molecules-29-02586-g001.jpg

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