结合的转录组和泛基因组分析指导代谢改善,以增强天菌素的生产
Jing Lin1, Yu Xiao1, Huiming Liu1
1Xiangya International Academy of Translational Medicine, Central South University, Yuelu District, Tongzipo Road, #172, Changsha, 410013, Hunan, China.
Applied microbiology and biotechnology
|January 3, 2024
概括
通过了解Streptomyces代谢,提高了高产量的抗生素生产. 加强脂肪酸降解显著提高了天胺素 (TNMs) 的产量,提高了药物开发潜力.
科学领域:
- 微生物生物技术 微生物生物技术
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
背景情况:
- 铁菌素 (TNM) 是具有治疗潜力的有价值的抗生素,但低产量标位限制了它们的应用.
- 识别高产率机制对于改善抗生素生产和促进药物开发至关重要.
研究的目的:
- 阐明高产菌株Streptomyces sp.内在的高产机制. CB03234-S. 这是一本书.
- 通过合理的代谢工程来增强天氏素 (TNMs) 产量.
主要方法:
- 用转录组,泛基因组和KEGG通路分析来了解代谢变化.
- 基因操纵,包括基因过度表达,用于加强特定的代谢途径.
- 对野生类型和人工菌株进行比较分析,以评估天菌素 (TNM) 产量.
主要成果:
- 发现RpsL (K43N) 突变赋予了 estreptomycin 耐药性,但没有增强 Tiancimycins (TNMs) 的产生.
- 改变碳和氨基酸代谢被确定为促进天胺素 (TNMs) 前体积累的关键因素.
- 脂肪酸降解基因的过度表达,特别是fadD,导致Tiancimycins (TNMs) 标位增加了63.2%,达到21.7 mg/L.
结论:
- 综合生物信息学分析有效地揭示了影响二次代谢产生的代谢途径.
- 有针对性的代谢工程,特别是增强脂肪酸降解,可以显著提高天胺素 (TNMs) 的产量.
- 这项研究为优化微生物菌株抗生素生产提供了一个框架.
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