维生素K2的生物合成及其甲萘醌基团合成酶的功能分析  

Biosynthesis of vitamin K2 and functional analysis of the biosynthetic enzymes involved in its menadione moiety

作　　者：张秋华 刘曼路 王峥[1] 张一鸣 苏海佳[1] ZHANG Qiuhua;LIU Manlu;WANG Zheng;ZHANG Yiming;SU Haijia(College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029,China)

机构地区：[1]北京化工大学生命科学与技术学院,北京100029

出　　处：《化工学报》2023年第1期342-354,共13页CIESC Journal

基　　金：国家重点研发计划项目(2021YFC2103600);国家自然科学基金项目(31961133018,21838001);江西省“双千计划”高层次创新团队项目(S2020CXTD0240)。

摘　　要：维生素K2(VK2)作为2-甲基-1,4-萘醌(简称甲萘醌)家族的衍生物,在预防骨质疏松和心血管钙化方面发挥着重要作用,随着其市场需求的日益增加,实现VK2产业化并降低生产成本成为大家关注的焦点。首先概述了VK2传统发酵工艺现状及面临的问题,之后详细分析了VK2生物合成途径及其基因工程改造策略,可以将枯草芽孢杆菌产量提高至1549.6 mg·L^(-1),产量是传统发酵菌株的7倍以上。此外,还围绕合成途径中经典甲萘醌骨架合成酶的功能及其蛋白结构进行汇总分析,通过对酶的蛋白结构、催化特异性和机理进行分析,揭示各个功能酶在VK2合成途径中发挥的作用及其内在关系。最后从合成生物学技术发展角度对VK2途径设计、构建与应用进行了展望,为提升VK2工业化产量提供理论参考。Vitamin K2(VK2),a derivative of the 2-methyl-1,4-naphthoquinone(menadione)family,plays an important role in the prevention of osteoporosis and cardiovascular calcification,and its increasing demand has aroused great interest to improve VK2 synthesis and reduce its manufacturing cost for industrial production.We first reviewed the status and some issues confronted in traditional microbial production of VK2.Then we presented its synthesis pathway and engineering efforts performed in recent studies and found that VK2 production could be greatly improved to 1549.6 mg·L^(-1)in Bacillus subtilis,which was more than 7 times higher than traditional microbial fermentation.Focusing on the synthesis pathway of 2-methyl-1,4-naphthoquinone,which constitutes as the conserved structure of VK2,we summarized the involved enzymes and analyzed their protein structure,catalytic specificity,and mechanism to reveal their roles in synthesis pathway and their internal relationship.Finally,the design,construction and application of VK2 pathway are prospected from the perspective of synthetic biology technology development,which provides a theoretical reference for improving the industrial production of VK2.

关 键 词：维生素K2 生物合成 甲萘醌 蛋白结构 

分 类 号：Q568[生物学—生物化学]