A bacterial cell factory converting glucose into scyllo-inositol, a therapeutic agent for Alzheimer's disease
A bacterial cell factory converting glucose into scyllo-inositol, a therapeutic agent for Alzheimer's disease
复制标题
DOI：
10.1038/s42003-020-0814-7
复制
发表时间：
2020-03-02
影响因子：
5.9
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
--
作者：
Michon, Christophe;Kang, Choong-Min;Yoshida, Ken-ichi
米琼等人。描述了使用重组枯草芽孢杆菌作为细胞工厂，能够从廉价的葡萄糖生产鲨肌醇，一种治疗阿尔茨海默病的化合物。他们证明它可以从 20 g L-1 葡萄糖中产生 2 g L-1 鲨肌醇。鲨肌醇是一种罕见的肌醇立体异构体，是一种治疗剂，在预防阿尔茨海默病方面显示出潜在功效。将编码肌醇-1-磷酸（MI1P）合酶（MI1PS）的结核分枝杆菌 ino1 引入枯草芽孢杆菌中，将葡萄糖-6-磷酸（G6P）转化为 MI1P。我们发现 pbuE 失活会升高细胞内 NAD(+) 中心点 NADH 的浓度，NADH 是 MI1PS 的重要辅助因子，并且是激活 MI1PS 所必需的。由此产生的 MI1P 通过内在肌醇单磷酸酶 YktC 去磷酸化为肌醇，随后通过先前建立的涉及两种肌醇脱氢酶 IolG 和 IolW 的人工途径异构化为鲨肌醇。此外，glcP和glcK均过表达，以提供更多的G6P并加速鲨肌醇的产生。因此，枯草芽孢杆菌细胞工厂被证明可以从 20 g L-1 葡萄糖生产 2 g L(-1) 鲨肌醇。这个细胞工厂提供了一种生产鲨肌醇的廉价方法，这将有助于我们应对老龄化社会中日益严重的阿尔茨海默病问题。
Michon et al. describe the use of a recombinant Bacillus subtilis as a cell factory capable of producing scyllo-inositol, a therapeutic compound for Alzheimer's disease, from inexpensive glucose. They demonstrate that it could produce 2 g L-1 of scyllo-inositol from 20 g L-1 glucose.A rare stereoisomer of inositol, scyllo-inositol, is a therapeutic agent that has shown potential efficacy in preventing Alzheimer's disease. Mycobacterium tuberculosis ino1 encoding myo-inositol-1-phosphate (MI1P) synthase (MI1PS) was introduced into Bacillus subtilis to convert glucose-6-phosphate (G6P) into MI1P. We found that inactivation of pbuE elevated intracellular concentrations of NAD(+)center dot NADH as an essential cofactor of MI1PS and was required to activate MI1PS. MI1P thus produced was dephosphorylated into myo-inositol by an intrinsic inositol monophosphatase, YktC, which was subsequently isomerized into scyllo-inositol via a previously established artificial pathway involving two inositol dehydrogenases, IolG and IolW. In addition, both glcP and glcK were overexpressed to feed more G6P and accelerate scyllo-inositol production. Consequently, a B. subtilis cell factory was demonstrated to produce 2 g L(-1)scyllo-inositol from 20 g L-1 glucose. This cell factory provides an inexpensive way to produce scyllo-inositol, which will help us to challenge the growing problem of Alzheimer's disease in our aging society.