Transcriptomics-guided optimization of vitamins to enhance erythromycin yield in saccharopolyspora erythraea.

IF 4.3 3区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Bioresources and Bioprocessing Pub Date : 2024-11-01 DOI:10.1186/s40643-024-00817-w
Xiang Ke, Xing Jiang, Shuohan Wang, Xiwei Tian, Ju Chu
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Abstract

Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96-12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale.

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转录组学指导下的维生素优化,提高囊孢菌红霉素产量。
比较转录组学发现,与野生型 NRRL 2338 相比,高产突变株 Saccharopolyspora erythraea HL3168 E3 中与辅因子和维生素代谢相关的基因表达模式截然不同。对九种维生素的作用进行了深入分析,确定焦磷酸硫胺素(TPP)、维生素B2、维生素B6、维生素B9、维生素B12和hemin是E3生产红霉素的关键促进剂,可使红霉素滴度提高7.96-12.66%。然后,应用 "普拉克特-伯曼设计 "和 "最陡上升路径 "进一步优化维生素组合,以获得最高的生产效率,使摇瓶中的红霉素滴度提高了 39.2%。此外,靶向代谢组学和代谢通量分析揭示了维生素补充如何调节中央碳代谢,对 TCA 循环和蛋氨酸合成产生显著影响,从而增加红霉素合成所必需的能量和前体物质的供应。这项工作凸显了精确补充维生素改善代谢途径,从而提高红霉素产量的能力,并为工业规模的应用提供了宝贵的方向。
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来源期刊
Bioresources and Bioprocessing
Bioresources and Bioprocessing BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
7.20
自引率
8.70%
发文量
118
审稿时长
13 weeks
期刊介绍: Bioresources and Bioprocessing (BIOB) is a peer-reviewed open access journal published under the brand SpringerOpen. BIOB aims at providing an international academic platform for exchanging views on and promoting research to support bioresource development, processing and utilization in a sustainable manner. As an application-oriented research journal, BIOB covers not only the application and management of bioresource technology but also the design and development of bioprocesses that will lead to new and sustainable production processes. BIOB publishes original and review articles on most topics relating to bioresource and bioprocess engineering, including: -Biochemical and microbiological engineering -Biocatalysis and biotransformation -Biosynthesis and metabolic engineering -Bioprocess and biosystems engineering -Bioenergy and biorefinery -Cell culture and biomedical engineering -Food, agricultural and marine biotechnology -Bioseparation and biopurification engineering -Bioremediation and environmental biotechnology
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