通过优化 DXS 表达和融合短链前炔基转移酶提高紫杉二烯的产量。

IF 4.5 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Siqi He, Anne-Sophie M.W. Bekhof, Eli Z. Popova, Ronald van Merkerk, Wim J. Quax
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引用次数: 0

摘要

本研究强调了过表达 MEP(4-磷酸赤藓醇)途径中的 1-脱氧-d-木酮糖-5-磷酸合成酶(DXS)以及短链前基转移酶融合物对提高二萜--紫杉醇生产中的第一个中间体--紫杉-4,11-二烯生产的重要意义。结果表明,(i) 将紫杉二烯合成酶(txs)基因整合到基因组中,(ii) 过量表达 MEP 途径基因,(iii) fpps-crtE 前酰转移酶融合蛋白,(iv) 额外表达 1-脱氧-d-木酮糖-5-磷酸合成酶(DXS)的菌株产生的紫杉-4,11-二烯产量最高,达到 390 毫克/升(26 毫克/升/OD600)。与报告的枯草芽孢杆菌中的最高浓度相比,增加了 13 倍。对 DXS 的额外过表达和利用短链前炔基转移酶融合物的关注强调了它们在显著提高萜烯生物合成的滴度方面的关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Improved taxadiene production by optimizing DXS expression and fusing short-chain prenyltransferases

Improved taxadiene production by optimizing DXS expression and fusing short-chain prenyltransferases

This study highlights the significance of overexpressing 1-deoxy-d-xylulose-5-phosphate synthase (DXS) from the MEP (methylerythritol 4-phosphate) pathway, in addition to short-chain prenyltransferase fusions for the improved production of the diterpene, taxa-4,11-diene, the first committed intermediate in the production of anti-cancer drug paclitaxel. The results showed that the strain which has (i) the taxadiene synthase (txs) gene integrated into the genome, (ii) the MEP pathway genes overexpressed, (iii) the fpps-crtE prenyltransferases fusion protein and (iv) additional expression of 1-deoxy-d-xylulose-5-phosphate synthase (DXS), yielded the highest production of taxa-4,11-diene at 390 mg/L (26 mg/L/OD600). This represents a thirteen-fold increase compared to the highest reported concentration in B. subtilis. The focus on additional overexpression of DXS and utilizing short-chain prenyltransferase fusions underscores their pivotal role in achieving significant titer improvements in terpene biosynthesis.

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来源期刊
New biotechnology
New biotechnology 生物-生化研究方法
CiteScore
11.40
自引率
1.90%
发文量
77
审稿时长
1 months
期刊介绍: New Biotechnology is the official journal of the European Federation of Biotechnology (EFB) and is published bimonthly. It covers both the science of biotechnology and its surrounding political, business and financial milieu. The journal publishes peer-reviewed basic research papers, authoritative reviews, feature articles and opinions in all areas of biotechnology. It reflects the full diversity of current biotechnology science, particularly those advances in research and practice that open opportunities for exploitation of knowledge, commercially or otherwise, together with news, discussion and comment on broader issues of general interest and concern. The outlook is fully international. The scope of the journal includes the research, industrial and commercial aspects of biotechnology, in areas such as: Healthcare and Pharmaceuticals; Food and Agriculture; Biofuels; Genetic Engineering and Molecular Biology; Genomics and Synthetic Biology; Nanotechnology; Environment and Biodiversity; Biocatalysis; Bioremediation; Process engineering.
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