Engineering Acinetobacter baylyi ADP1 for mevalonate production from lignin-derived aromatic compounds

IF 3.7 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Metabolic Engineering Communications Pub Date : 2021-12-01 DOI:10.1016/j.mec.2021.e00173
Erika Arvay , Bradley W. Biggs , Laura Guerrero , Virginia Jiang , Keith Tyo
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引用次数: 12

Abstract

Utilization of lignin, an abundant renewable resource, is limited by its heterogenous composition and complex structure. Biological valorization of lignin provides advantages over traditional chemical processing as it occurs at ambient temperature and pressure and does not use harsh chemicals. Furthermore, the ability to biologically funnel heterogenous substrates to products eliminates the need for costly downstream processing and separation of feedstocks. However, lack of relevant metabolic networks and low tolerance to degradation products of lignin limits the application of traditional engineered model organisms. To circumvent this obstacle, we employed Acinetobacter baylyi ADP1, which natively catabolizes lignin-derived aromatic substrates through the β-ketoadipate pathway, to produce mevalonate from lignin-derived compounds. We enabled expression of the mevalonate pathway in ADP1 and validated activity in the presence of multiple lignin-derived aromatic substrates. Furthermore, by knocking out wax ester synthesis and utilizing fed-batch cultivation, we improved mevalonate titers 7.5-fold to 1014 mg/L (6.8 mM). This work establishes a foundation and provides groundwork for future efforts to engineer improved production of mevalonate and derivatives from lignin-derived aromatics using ADP1.

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工程贝氏不动杆菌ADP1从木质素衍生的芳香族化合物生产甲羟戊酸
木质素是一种丰富的可再生资源,但其组成的异质性和结构的复杂性限制了其利用。与传统的化学处理相比,木质素的生物增值具有优势,因为它是在环境温度和压力下进行的,并且不使用刺激性化学品。此外,生物漏斗异质底物到产品的能力消除了昂贵的下游加工和原料分离的需要。然而,缺乏相关的代谢网络和对木质素降解产物的低耐受性限制了传统工程模式生物的应用。为了克服这一障碍,我们利用baylyi不动杆菌ADP1,它通过β-酮己二酸途径天然分解木质素衍生的芳香底物,从木质素衍生的化合物中产生甲羟戊酸。我们在ADP1中激活了甲羟戊酸途径的表达,并在多种木质素衍生的芳香底物存在下验证了其活性。此外,通过敲除蜡酯合成并利用补料分批培养,我们将甲羟戊酸滴度提高了7.5倍,达到1014 mg/L(6.8 mM)。这项工作为未来利用ADP1改进木质素衍生芳烃的甲羟戊酸及其衍生物的生产奠定了基础和基础。
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来源期刊
Metabolic Engineering Communications
Metabolic Engineering Communications Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
13.30
自引率
1.90%
发文量
22
审稿时长
18 weeks
期刊介绍: Metabolic Engineering Communications, a companion title to Metabolic Engineering (MBE), is devoted to publishing original research in the areas of metabolic engineering, synthetic biology, computational biology and systems biology for problems related to metabolism and the engineering of metabolism for the production of fuels, chemicals, and pharmaceuticals. The journal will carry articles on the design, construction, and analysis of biological systems ranging from pathway components to biological complexes and genomes (including genomic, analytical and bioinformatics methods) in suitable host cells to allow them to produce novel compounds of industrial and medical interest. Demonstrations of regulatory designs and synthetic circuits that alter the performance of biochemical pathways and cellular processes will also be presented. Metabolic Engineering Communications complements MBE by publishing articles that are either shorter than those published in the full journal, or which describe key elements of larger metabolic engineering efforts.
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