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利用... 进行反式,顺- 乌头酸生产的代谢工程和过程强化。

Metabolic Engineering and Process Intensification for Muconic Acid Production Using .

机构信息

Centre for Industrial Biotechnology and Biocatalysis (InBio.be), Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

Bio Base Europe Pilot Plant (BBEPP), 9042 Ghent, Belgium.

出版信息

Int J Mol Sci. 2024 Sep 24;25(19):10245. doi: 10.3390/ijms251910245.

DOI:10.3390/ijms251910245
PMID:39408575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11476194/
Abstract

The efficient production of biobased organic acids is crucial to move to a more sustainable and eco-friendly economy, where muconic acid is gaining interest as a versatile platform chemical to produce industrial building blocks, including adipic acid and terephthalic acid. In this study, a platform strain able to convert glucose and xylose into ,-muconic acid was further engineered to eliminate C2 dependency, improve muconic acid tolerance, enhance production and growth performance, and substantially reduce the side production of the intermediate protocatechuic acid. This was achieved by reintroducing the gene and overexpression of genes. The improved strain was integrated in low-pH fed-batch fermentations at bioreactor scale with integrated product recovery. By adding a biocompatible organic phase consisting of CYTOP 503 and canola oil to the process, a continuous extraction of muconic acid was achieved, resulting in significant alleviation of product inhibition. Through this, the muconic acid titer and peak productivity were improved by 300% and 185%, respectively, reaching 9.3 g/L and 0.100 g/L/h in the product recovery process as compared to 3.1 g/L and 0.054 g/L/h in the control process without ISPR.

摘要

高效生产生物基有机酸对于向更加可持续和环保的经济转型至关重要,其中壬二酸作为一种多功能的平台化学品,正在引起人们的兴趣,可用于生产工业建筑模块,包括己二酸和对苯二甲酸。在本研究中,进一步工程改造了一种能够将葡萄糖和木糖转化为,-壬二酸的平台菌株,以消除对 C2 的依赖性、提高壬二酸耐受性、增强生产和生长性能,并显著减少中间产物原儿茶酸的副产物生成。这是通过重新引入 基因和过表达 基因实现的。改良后的菌株在生物反应器规模的低 pH 分批补料发酵中进行了整合,同时进行了集成产物回收。通过向该过程中添加由 CYTOP 503 和菜籽油组成的生物相容性有机相,实现了壬二酸的连续提取,从而显著缓解了产物抑制。通过这种方式,与没有 ISPR 的对照过程相比,在产物回收过程中,壬二酸的浓度和峰值生产力分别提高了 300%和 185%,达到 9.3 g/L 和 0.100 g/L/h。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/6e7d07e4661a/ijms-25-10245-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/21163a9b6933/ijms-25-10245-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/815b1c745cdc/ijms-25-10245-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/36e087e563fb/ijms-25-10245-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/2fcc62dbb5a4/ijms-25-10245-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/6e7d07e4661a/ijms-25-10245-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/21163a9b6933/ijms-25-10245-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/815b1c745cdc/ijms-25-10245-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/36e087e563fb/ijms-25-10245-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/2fcc62dbb5a4/ijms-25-10245-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2961/11476194/6e7d07e4661a/ijms-25-10245-g005.jpg

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