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通过组学分析结合发酵优化提高维生素 B 产量。

Enhancement of vitamin B production driven by omics analysis combined with fermentation optimization.

机构信息

College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, China.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.

出版信息

Microb Cell Fact. 2024 May 15;23(1):137. doi: 10.1186/s12934-024-02405-1.

Abstract

BACKGROUND

Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B for various applications. Numerous microorganisms naturally produce vitamin B, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B poses a challenge in constructing an efficient cell factory.

RESULTS

In this study, we conducted transcriptome and metabolome analyses to investigate the effects of the accumulation of pyridoxine, which is the major commercial form of vitamin B, on cellular processes in Escherichia coli. Our omics analysis revealed associations between pyridoxine and amino acids, as well as the tricarboxylic acid (TCA) cycle. Based on these findings, we identified potential targets for fermentation optimization, including succinate, amino acids, and the carbon-to-nitrogen (C/N) ratio. Through targeted modifications, we achieved pyridoxine titers of approximately 514 mg/L in shake flasks and 1.95 g/L in fed-batch fermentation.

CONCLUSION

Our results provide insights into pyridoxine biosynthesis within the cellular metabolic network for the first time. Our comprehensive analysis revealed that the fermentation process resulted in a remarkable final yield of 1.95 g/L pyridoxine, the highest reported yield to date. This work lays a foundation for the green industrial production of vitamin B in the future.

摘要

背景

微生物工程旨在提高细菌生产有价值产品的能力,包括各种应用的维生素 B。许多微生物天然产生维生素 B,但涉及的代谢途径受到严格控制。这种维生素 B 的积累所带来的调节对构建高效细胞工厂构成了挑战。

结果

在这项研究中,我们进行了转录组和代谢组分析,以研究吡哆醇(维生素 B 的主要商业形式)积累对大肠杆菌细胞过程的影响。我们的组学分析揭示了吡哆醇与氨基酸以及三羧酸 (TCA) 循环之间的关联。基于这些发现,我们确定了发酵优化的潜在目标,包括琥珀酸、氨基酸和碳氮比。通过有针对性的修饰,我们在摇瓶中实现了约 514mg/L 的吡哆醇产量和补料分批发酵中的 1.95g/L 产量。

结论

我们的结果首次提供了细胞代谢网络内吡哆醇生物合成的见解。我们的综合分析表明,发酵过程的最终产率达到了 1.95g/L 的吡哆醇,这是迄今为止报道的最高产率。这项工作为未来维生素 B 的绿色工业生产奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc69/11095007/5c3c8aa18a06/12934_2024_2405_Fig1_HTML.jpg

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