Integrated intracellular metabolic profiling and pathway analysis approaches reveal complex metabolic regulation by Clostridium acetobutylicum.
Integrated intracellular metabolic profiling and pathway analysis approaches reveal complex metabolic regulation by Clostridium acetobutylicum.
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综合细胞内代谢谱和通路分析方法揭示了丙酮丁醇梭菌复杂的代谢调节
DOI：
10.1186/s12934-016-0436-4
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发表时间：
2016-02-15
影响因子：
6.4
通讯作者：
Wen J
中科院分区：
文献类型：
--
作者：
Liu H;Huang D;Wen J
背景：丙酮丁醇梭菌是重要的丁醇生产菌之一。然而，发酵过程中的环境胁迫通常导致产量较低，严重阻碍了其工业化。结果：采用气相色谱-质谱联用技术、偏最小二乘判别分析和途径分析相结合的方法，共鉴定出40条代谢途径，涉及43个关键代谢节点。深入分析表明，大量氨基酸代谢促进细胞生长，但对丁醇合成影响不大;糖代谢有利于细胞生长，但不利于丁醇合成。此外，赖氨酸和琥珀酸的代谢对整个代谢网络产生了复杂的影响。二羧酸代谢对细胞生长和丁醇合成起着不可或缺的作用。随后，提出了合理的补料策略，以验证这些结论，促进丁醇的生物合成。结论：代谢谱结合途径分析方法为探索细胞代谢活性提供了一种准确、合理、实用的方法，为提高丁醇产量提供了依据。这些策略也可以扩展到生产其他重要的生物化学化合物。
Background:Clostridium acetobutylicum is one of the most important butanol producing strains. However, environmental stress in the fermentation process usually leads to a lower yield, seriously hampering its industrialization. In order to systematically investigate the key intracellular metabolites that influence the strain growth and butanol production, and find out the critical regulation nodes, an integrated analysis approach has been carried out in this study.Results:Based on the gas chromatography-mass spectrometry technology, the partial least square discriminant analysis and the pathway analysis, 40 metabolic pathways linked with 43 key metabolic nodes were identified. In-depth analysis showed that lots of amino acids metabolism promoted cell growth but exerted slight influence on butanol production, while sugar metabolism was favorable for cell growth but unfavorable for butanol synthesis. Besides, both lysine and succinic acid metabolism generated a complex effect on the whole metabolic network. Dicarboxylate metabolism exerted an indispensable role on cell growth and butanol production. Subsequently, rational feeding strategies were proposed to verify these conclusions and facilitate the butanol biosynthesis. Feeding amino acids, especially glycine and serine, could obviously improve cell growth while yeast extract, citric acid and ethylene glycol could significantly enhance both growth and butanol production.Conclusions:The feeding experiment confirmed that metabolic profiling combined with pathway analysis provided an accurate, reasonable and practical approach to explore the cellular metabolic activity and supplied a basis for improving butanol production. These strategies can also be extended for the production of other important bio-chemical compounds.