Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids
Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids
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DOI：
10.1021/acssynbio.5b00201
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发表时间：
2016-03-01
影响因子：
4.7
通讯作者：
Zhang, Fuzhong
中科院分区：
文献类型：
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作者：
Bowen, Christopher H.;Bonin, Jeff;Zhang, Fuzhong
为了寻找可持续的塑料生产方法，已经做出了许多努力来设计微生物将可再生原料转化为短链（C2-C8）双功能聚合物前体（例如，琥珀酸，尸胺，1,4-丁二醇）。中链（C12-C14）单体，如ω -羟基脂肪酸（ω - ohfas）和α， ω -二羧酸（α, ω - dcas），很少受到关注，它们是高性能聚酯和聚酰胺的前体。在这里，我们设计了一个完整的微生物将葡萄糖转化为C12和C14 omega-OHFAs和α，omega-DCAs，并精确控制产物链的长度。使用扩展的生物信息学方法，我们筛选跨门的广泛酶，以确定产生完全转化的中间体到产品α，omega-DCAs的组合。最后，通过优化培养条件，将C12 α、omega-DCA的生产滴度提高到接近600 mg/L。我们的研究结果表明，该微生物工厂有潜力实现具有商业意义的、可再生的C12 α、omega-DCA的生产，这是高性能塑料尼龙-6,12的宝贵前体。
In search of sustainable approaches to plastics production, many efforts have been made to engineer microbial conversions of renewable feedstock to short-chain (C2-C8) bifunctional polymer precursors (e.g., succinic acid, cadaverine, 1,4-butanediol). Less attention has been given to medium-chain (C12-C14) monomers such as omega-hydroxy fatty acids (omega-OHFAs) and alpha,omega-dicarboxylic acids (alpha,omega-DCAs), which are precursors to high performance polyesters and polyamides. Here we engineer a complete microbial conversion of glucose to C12 and C14 omega-OHFAs and alpha,omega-DCAs, with precise control of product chain length. Using an expanded bioinformatics approach, we screen a wide range of enzymes across phyla to identify combinations that yield complete conversion of intermediates to product alpha,omega-DCAs. Finally, through optimization of culture conditions, we enhance production titer of C12 alpha,omega-DCA to nearly 600 mg/L. Our results indicate potential for this microbial factory to enable commercially relevant, renewable production of C12 alpha,omega-DCA a valuable precursor to the high-performance plastic, nylon-6,12.