Expanding metabolism for biosynthesis of nonnatural alcohols
Expanding metabolism for biosynthesis of nonnatural alcohols
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DOI：
10.1073/pnas.0807157106
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发表时间：
2008-12-30
影响因子：
11.1
通讯作者：
Liao, James C.
中科院分区：
文献类型：
--
作者：
Zhang, Kechun;Sawaya, Michael R.;Liao, James C.
大自然使用有限的代谢物来完成所有的生化反应。为了提高生物系统的代谢能力，我们使用非天然代谢工程方法扩展了天然代谢网络。通过工程化2-异丙基苹果酸合酶的链延伸活性和通过合理的蛋白质设计改变下游酶的底物特异性，支链氨基酸途径被延伸以产生非生物的较长链酮酸和醇。当引入大肠杆菌时，这种非天然的生物合成途径产生各种碳数从5到8的长链醇。特别是，我们通过优化6-碳醇（S）-3-甲基-1-戊醇的生物合成来证明这种方法的可行性。这项工作展示了一种超越自然代谢网络建立人工代谢的方法。非天然代谢物，如长链醇，现在包括在生命系统的代谢物家族。
Nature uses a limited set of metabolites to perform all of the biochemical reactions. To increase the metabolic capabilities of biological systems, we have expanded the natural metabolic network, using a nonnatural metabolic engineering approach. The branched-chain amino acid pathways are extended to produce abiotic longer chain keto acids and alcohols by engineering the chain elongation activity of 2-isopropylmalate synthase and altering the substrate specificity of downstream enzymes through rational protein design. When introduced into Escherichia coli, this nonnatural biosynthetic pathway produces various long-chain alcohols with carbon number ranging from 5 to 8. In particular, we demonstrate the feasibility of this approach by optimizing the biosynthesis of the 6-carbon alcohol, (S)-3-methyl-1-pentanol. This work demonstrates an approach to build artificial metabolism beyond the natural metabolic network. Nonnatural metabolites such as long chain alcohols are now included in the metabolite family of living systems.