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工程化大肠杆菌提高(R)-1,3-丁二醇的产量。

Improvement of (R)-1,3-butanediol production by engineered Escherichia coli.

机构信息

Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Hiroshima 739-8530, Japan.

出版信息

J Biosci Bioeng. 2013 May;115(5):475-80. doi: 10.1016/j.jbiosc.2012.11.025. Epub 2013 Jan 4.

DOI:10.1016/j.jbiosc.2012.11.025
PMID:23290993
Abstract

(R)-1,3-Butanediol is a valuable chemical extensively used as a key intermediate for the synthesis of pharmaceuticals and several industrial compounds. Despite its high demand, the production has been restricted from multi-step chemical production, petrochemical substrate requirement and a non-existence natural synthesis pathway from renewable biomass. In this study, an artificial synthesis route was genetically engineered in Escherichia coli MG1655 lacI(q) to produce 1,3-butanediol from glucose. The selection of heterologous genes from several organisms and activity level of their corresponding gene products were demonstrated to be the key element for the product formation. Improvement of fermentation aeration and the application of fed-batch system significantly enhanced 1,3-butanediol production. Under the optimized conditions, 1,3-butanediol was produced up to 9.05 g/l (100.4 mM) with 98.5 ± 0.2% enantiomeric excess (% ee) of (R)-1,3-butanediol. This is the highest yield of 1,3-butanediol produced from glucose with the highest optical purity by the recombinant strain reported thus far.

摘要

(R)-1,3-丁二醇是一种有价值的化学品,被广泛用作合成药物和几种工业化合物的关键中间体。尽管需求量很大,但由于多步化学生产、石化原料要求以及可再生生物质中不存在天然合成途径,其生产受到限制。在本研究中,通过基因工程在大肠杆菌 MG1655 lacI(q) 中构建了一条人工合成途径,从葡萄糖生产 1,3-丁二醇。来自几种生物体的异源基因的选择及其相应基因产物的活性水平被证明是产物形成的关键因素。发酵通气的改善和补料分批系统的应用显著提高了 1,3-丁二醇的产量。在优化条件下,1,3-丁二醇的产量高达 9.05 g/L(100.4 mM),(R)-1,3-丁二醇的对映体过量(ee)为 98.5±0.2%。这是迄今为止报道的重组菌株从葡萄糖生产的 1,3-丁二醇的最高产量和最高光学纯度。

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