在酵母酵母中解码和重新编程由衍生的生物活性II型甘酸的生物合成网络
Qin Wang1, Ye Li1, Shunhan Zhang1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Cell discovery
|July 7, 2025
概括
这项研究解读了Ganoderma lucidum中II型甘酸 (TIIGAs) 的生物合成途径,使这些有价值的代谢物的增强生产成为可能. 重编程生物合成网络显著提高了TIIGA产量,用于潜在的制药应用.
科学领域:
- 菌类学 菌类学是指菌类学.
- 生物化学 生物化学
- 代谢工程是代谢工程.
背景情况:
- 的特殊代谢物,如甘酸,具有显著的药理潜力.
- 阐明和重编程菌生物合成途径以产生向代谢物仍然是一个重大挑战.
研究的目的:
- 解码Ganoderma lucidum中II型甘酸 (TIIGA) 的生物合成网络.
- 确定参与TIIGA生物合成的关键酶,包括负责化和乙化的酶.
- 通过代谢重编程来设计增强的TIIGA生产.
主要方法:
- 研究了Ganoderma lucidum中的协调基因表达.
- 识别和表征了用于C22化,C3配置转换和C3/C15/C22乙化的酶.
- 采用光引导的整合方法,以实现高效的生物合成.
- 使用面包酵母作为TIIGA生产的异质宿主.
- 通过暂时调节乙转移酶表达来疏代谢块.
主要成果:
- 解码了TIIGA的生物合成途径,识别了诸如CYP512W6和双功能乙转移酶GLAT.等关键酶.
- 使用光引导方法实现了TIIGA的有效工业规模生物合成.
- 在工程制造的面包酵母中成功生产了30多个TIIGA,其标位比培养的高出1-4个数量级.
- 通过对基因表达的时间调节,克服异质宿主中的代谢瓶.
结论:
- 这项工作为Ganoderma lucidum中TIIGA生物合成提供了全面的理解.
- 对TIIGA生物合成网络的重新编程可以显著提高价值的代谢物的生产.
- 这些发现促进了对TIIGA的广泛应用,并为其他真菌代谢物研究提供了洞察力.
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