在Serratia marcescens中的混合甲基养途径,用于可持续的类生物合成
Di Liu1, Long Wang1, Linbo Gou1
1The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
ACS synthetic biology
|April 10, 2025
概括
这项研究在Serratia marcescens中设计了一个以甲醇为基础的途径,用于生产有价值的类. 工程微生物高效地将甲醇转化为日列和 (-) -α-bisabolol,证明了一种新的生物生产途径.
科学领域:
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
- 工业生物技术 工业生物技术
背景情况:
- 类是价值高的化合物,具有多样化的工业应用.
- 甲醇为化学生产提供了一个环保的,非糖原料.
- 塞拉蒂亚marcescens HBQA7对甲醇和类药物表现出耐受性,使其成为合适的宿主生物体.
研究的目的:
- 在 *Serratia marcescens* 中设计一种混合甲基转化途径,用于从甲醇中进行类生物合成.
- 优化甲醇利用和美酸盐 (MVA) 途径,以提高产量.
- 为了证明使用甲醇作为唯一的碳来源生产单烯和六烯的可行性.
主要方法:
- 通过使用细菌甲醇脱酶 (Mdh) 和酵母二基合成酶 (Das) 设计了一种混合甲基转化途径.
- 利用C标记实验来确定最佳的酶对和代谢中间体.
- 在酸通路 (rpiAB) 中进行基因删除,以增强甲醇同化.
- 优化了美酸盐 (MVA) 生物合成途径,并构建了一个光类型的MVA途径.
主要成果:
- 确定了最佳的Mdh (Acinetobacter gerneri) 和Das (Pichia angusta) 酶,在酸盐中达到7.63%的C缩.
- 通过rpiAB删除增强的甲醇利用导致了22.99%的13C缩.
- 从甲醇和氧化糖中实现了5.12g/L的美瓦酸盐生产.
- 在摇瓶培养中生产的基拉尼 (574.12 mg/L) 和 (-) -α-比萨博 (1256.41 mg/L).
结论:
- 在Serratia marcescens中首次成功演示了甲醇转化为有价值的类.
- 工程化途径和优化的宿主菌株为化物生产提供了一个新的和可持续的平台.
- 这种方法为传统方法提供了有希望的替代方案,使用环保原料.
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