Improvement in L-ornithine production from mannitol via transcriptome-guided genetic engineering in Corynebacterium glutamicum.

Libin Nie, Yutong He, Lirong Hu, Xiangdong Zhu, Xiaoyu Wu, Bin Zhang
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Abstract

Background: L-Ornithine is an important medicinal intermediate that is mainly produced by microbial fermentation using glucose as the substrate. To avoid competition with human food resources, there is an urgent need to explore alternative carbon sources for L-ornithine production. In a previous study, we constructed an engineered strain, Corynebacterium glutamicum MTL13, which produces 54.56 g/L of L-ornithine from mannitol. However, compared with the titers produced using glucose as a substrate, the results are insufficient, and further improvement is required.

Results: In this study, comparative transcriptome profiling of MTL01 cultivated with glucose or mannitol was performed to identify novel targets for engineering L-ornithine-producing strains. Guided by the transcriptome profiling results, we modulated the expression of qsuR (encoding a LysR-type regulator QsuR), prpC (encoding 2-methylcitrate synthase PrpC), pdxR (encoding a MocR-type regulator PdxR), acnR (encoding a TetR-type transcriptional regulator AcnR), CGS9114_RS08985 (encoding a hypothetical protein), and CGS9114_RS09730 (encoding a TetR/AcrR family transcriptional regulator), thereby generating the engineered strain MTL25 that can produce L-ornithine at a titer of 93.6 g/L, representing a 71.6% increase as compared with the parent strain MTL13 and the highest L-ornithine titer reported so far for C. glutamicum.

Conclusions: This study provides novel indirect genetic targets for enhancing L-ornithine accumulation on mannitol and lays a solid foundation for the biosynthesis of L-ornithine from marine macroalgae, which is farmed globally as a promising alternative feedstock.

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通过谷氨酸棒杆菌转录组引导的基因工程改善甘露醇中 L-鸟氨酸的生产。
背景:L-鸟氨酸是一种重要的药用中间体,主要是以葡萄糖为底物通过微生物发酵生产的。为避免与人类食物资源竞争,迫切需要探索生产 L-鸟氨酸的替代碳源。在之前的研究中,我们构建了一株谷氨酸棒状杆菌(Corynebacterium glutamicum MTL13)工程菌株,它能从甘露醇中产生 54.56 克/升的 L-鸟氨酸。然而,与以葡萄糖为底物产生的滴度相比,结果还不够理想,需要进一步改进:结果:本研究对使用葡萄糖或甘露醇培养的 MTL01 进行了转录组比较分析,以确定培养 L-鸟氨酸生产菌株的新靶标。在转录组分析结果的指导下,我们调节了 qsuR(编码 LysR 型调节因子 QsuR)、prpC(编码 2-甲基柠檬酸合成酶 PrpC)、pdxR(编码 MocR 型调节因子 PdxR)、acnR(编码 TetR 型转录调节因子 AcnR)的表达、CGS9114_RS08985(编码一个假说蛋白)和 CGS9114_RS09730(编码一个 TetR/AcrR 家族转录调控因子),从而产生了可生产 L-鸟氨酸的工程菌株 MTL25,其滴度为 93.6 g/L,与亲本菌株 MTL13 相比提高了 71.6%,是迄今为止谷氨酸棒状杆菌 L-鸟氨酸滴度最高的菌株:这项研究为提高 L-鸟氨酸在甘露醇上的积累提供了新的间接遗传目标,并为从海洋大型藻类中生物合成 L-鸟氨酸奠定了坚实的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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