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首页> 外文期刊>BMC Biotechnology >Metabolic evolution of Corynebacterium glutamicum for increased production of L-ornithine
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Metabolic evolution of Corynebacterium glutamicum for increased production of L-ornithine

机译：谷氨酸棒杆菌的代谢进化，提高了L-鸟氨酸的产量

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Background L-ornithine is effective in the treatment of liver diseases and helps strengthen the heart. The commercial applications mean that efficient biotechnological production of L-ornithine has become increasingly necessary. Adaptive evolution strategies have been proven a feasible and efficient technique to achieve improved cellular properties without requiring metabolic or regulatory details of the strain. The evolved strains can be further optimised by metabolic engineering. Thus, metabolic evolution strategy was used for engineering Corynebacterium glutamicum to enhance L-ornithine production. Results A C. glutamicum strain was engineered by using a combination of gene deletions and adaptive evolution with 70 passages of growth-based selection. The metabolically evolved C. glutamicum strain, named ΔAPE6937R42, produced 24.1 g/L of L-ornithine in a 5-L bioreactor. The mechanism used by C. glutamicum ΔAPE6937R42 to produce L-ornithine was investigated by analysing transcriptional levels of select genes and NADPH contents. The upregulation of the transcription levels of genes involved in the upstream pathway of glutamate biosynthesis and the elevated NADPH concentration caused by the upregulation of the transcriptional level of the ppnK gene promoted L-ornithine production in C. glutamicum ΔAPE6937R42. Conclusions The availability of NADPH plays an important role in L-ornithine production in C. glutamicum. Our results demonstrated that the combination of growth-coupled evolution with analysis of transcript abundances provides a strategy to engineer microbial strains for improving production of target compounds.
机译：背景技术L-鸟氨酸可有效治疗肝脏疾病并有助于增强心脏。商业应用意味着有效的生物技术生产左旋鸟氨酸变得越来越必要。适应性进化策略已被证明是一种可行且有效的技术，可在不要求菌株代谢或调节细节的情况下实现改善的细胞特性。可以通过代谢工程进一步优化进化的菌株。因此，代谢进化策略被用于工程化谷氨酸棒杆菌以增强L-鸟氨酸的产生。结果谷氨酸棒杆菌菌株是通过基因缺失和适应性进化相结合的方法进行工程改造的，其中有70代基于生长的选择。代谢进化的谷​​氨酸棒杆菌菌株ΔAPE6937R42在5升生物反应器中产生24.1克/升的L-鸟氨酸。通过分析选择基因的转录水平和NADPH含量，研究了谷氨酸棒杆菌ΔAPE6937R42产生L-鸟氨酸的机理。谷氨酸生物合成上游途径中涉及的基因转录水平的上调和ppnK基因转录水平上调引起的NADPH浓度升高促进了谷氨酸棒杆菌ΔAPE6937R42中L-鸟氨酸的产生。结论NADPH的可用性在谷氨酸棒杆菌的L-鸟氨酸生产中起重要作用。我们的结果表明，生长耦合进化与转录本丰度分析的结合提供了一种工程改造微生物菌株以提高目标化合物产量的策略。

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