Engineering nonphosphorylative metabolism to generate lignocellulose-derived products

Engineering nonphosphorylative metabolism to generate lignocellulose-derived products
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DOI:
10.1038/nchembio.2020
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发表时间:
2016-04-01
影响因子:
14.8
通讯作者:
Zhang, Kechun
Zhang, Kechun
中科院分区:
生物学1区
文献类型:
--
作者:
Tai, Yi-Shu;Xiong, Mingyong;Zhang, Kechun

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将木质纤维素生物质转化为增值产品提供了重要的环境和经济效益。本文报道了d -木糖、l -阿拉伯糖和d -半乳糖酸三羧酸(TCA)循环衍生物的非常规代谢工程。我们设计了一个基于生长的选择平台,以鉴定大肠杆菌中具有功能的几个基因簇,这些基因簇可以在不到6步的时间内将糖非磷酸化同化到TCA循环中。为了证明这一新代谢平台的应用,我们建立了1,4-丁二醇(BDO)的人工生物合成途径,理论摩尔产率为100%。通过对下游途径酶2-酮酸脱羧酶和醇脱氢酶的筛选和工程设计,我们构建了能够从d -木糖、l -阿拉伯糖和d -半乳糖酸中生产BDO的大肠杆菌菌株。该方法的滴度、速率和产率均高于以往报道的传统途径。这项工作证明了非磷酸化代谢在提高生物合成效率的生物制造中的潜力。
Conversion of lignocellulosic biomass into value-added products provides important environmental and economic benefits. Here we report the engineering of an unconventional metabolism for the production of tricarboxylic acid (TCA)-cycle derivatives from D-xylose, L-arabinose and D-galacturonate. We designed a growth-based selection platform to identify several gene clusters functional in Escherichia coli that can perform this nonphosphorylative assimilation of sugars into the TCA cycle in less than six steps. To demonstrate the application of this new metabolic platform, we built artificial biosynthetic pathways to 1,4-butanediol (BDO) with a theoretical molar yield of 100%. By screening and engineering downstream pathway enzymes, 2-ketoacid decarboxylases and alcohol dehydrogenases, we constructed E. coli strains capable of producing BDO from D-xylose, L-arabinose and D-galacturonate. The titers, rates and yields were higher than those previously reported using conventional pathways. This work demonstrates the potential of nonphosphorylative metabolism for biomanufacturing with improved biosynthetic efficiencies.