通过工程增强的menaquinone生物合成2-Succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate Synthase MenD,以减轻Bacillus
Xian Sun1,2, Yangyang Li1,2, Lei Xing3
1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China.
ACS synthetic biology
|August 28, 2025
概括
研究人员通过设计MenD酶来增强维生素K2 (menaquinones, MKs) 的产生. 这克服了反抑制,提高了MK-7产量22. 3%,改善了骨和心血管健康应用.
科学领域:
- 生物技术
- 代谢工程
- 酶工程
背景情况:
- 维生素K2对于骨和心血管健康至关重要.
- 由于途径瓶和反抑制,MKs的微生物产生受到限制.
- 1,4-二二酸 (DHNA) 抑制了MK通路中的MenD酶.
研究的目的:
- 为了克服对MenD酶的DHNA反抑制.
- 为了增强微生物的menaquinone-7 (MK-7).
主要方法:
- 确定DHNA是MenD的反抑制剂.
- 采用结构引导进化来创建一个反耐药的MenD变体 (MenDW322I/R323F).
- 使用分子动力学 (MD) 模拟来分析酶抑制剂相互作用.
主要成果:
- 开发了一种MenD变种,其活性高出43%,并且对DHNA有抗性.
- 在MK-7的产量增加了22.3%,达到186.5mg/L.
- MD模拟证实突变酶与DHNA之间的相互作用减弱.
结论:
- 成功设计了MenD以克服DHNA的反抑制.
- 这种策略显著提高了MK-7微生物的生产效率.
- 为优化工业应用MKs生物合成提供了基础.
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