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在代谢工程酿酒酵母中合成己二酸。

Biosynthesis of adipic acid in metabolically engineered Saccharomyces cerevisiae.

机构信息

National Engineering Laboratory for Cereal Fermentation Technology (NELCF), School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, P. R. China.

School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, P. R. China.

出版信息

J Microbiol. 2020 Dec;58(12):1065-1075. doi: 10.1007/s12275-020-0261-7. Epub 2020 Oct 23.

DOI:10.1007/s12275-020-0261-7
PMID:33095385
Abstract

Adipic Acid (AA) is a valued platform chemical compound, which can be used as a precursor of nylon-6,6. Due to the generation of an enormous amount of nitric oxide metabolites and the growing depletion of oil resources as a result of AA production from a mixture of cyclohexanol and cyclohexanone, the microbial methods for synthesizing AA have attracted significant attention. Of the several AA-producing pathways, the reverse adipate degradation pathway in Thermobifida fusca (Tfu RADP) is reported to be the most efficient, which has been confirmed in Escherichia coli. In this study, the heterologous Tfu RADP was constructed for producing AA in S. cerevisiae by co-expressing genes of Tfu_0875, Tfu_2399, Tfu_0067, Tfu_1647, Tfu_2576, and Tfu_2576. The AA titer combined with biomass, cofactors and other by-products was all determined after fermentation. During batch fermentation in a shake flask, the maximum AA titer was 3.83 mg/L, while the titer increased to 10.09 mg/L during fed-batch fermentation in a 5-L bioreactor after fermentation modification.

摘要

己二酸(AA)是一种有价值的平台化合物,可用作尼龙-6,6 的前体。由于从环己醇和环己酮混合物中生产 AA 会产生大量的一氧化氮代谢物,并且由于石油资源的日益枯竭,微生物合成 AA 的方法引起了广泛关注。在几种 AA 生产途径中,报道表明Thermobifida fusca(Tfu RADP)中的反式己二酸降解途径是最有效的,这已在大肠杆菌中得到证实。在这项研究中,通过共表达 Tfu_0875、Tfu_2399、Tfu_0067、Tfu_1647、Tfu_2576 和 Tfu_2576 的基因,构建了异源 Tfu RADP 以在酿酒酵母中生产 AA。发酵后测定 AA 产量与生物量、辅因子和其他副产物的总和。在摇瓶分批发酵过程中,AA 的最大产量为 3.83mg/L,而在 5L 生物反应器中进行分批补料发酵后,经过发酵改良,AA 的产量增加到 10.09mg/L。

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