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A Bacillus subtilis cell factory for producing scyllo-inositol, a disease-modifying therapeutic agent for Alzheimer's disease

机译:枯草芽孢杆菌细胞厂用于生产Scyllo-inositol,一种用于阿尔茨海默病的疾病改性治疗剂

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We previously demonstrated a prototype of a cell factory, which enables conversion from myo-inositol (MI) to scyllo-inositol (SI), using a strain of Bacillus subtilis with the modified inositol metabolic pathway. However, it wasted half of the MI, and the conversion rate was limited to only 40-50%. In this study all 'useless' genes involved in MI and SI metabolism were deleted, and MI was not wasted in the new strain though no elevation in SI production was achieved. IolG and IolW are the key enzymes responsible for the conversion. Overexpression of IolG and IolW was attempted for the further elevation in the conversion rate, the rate reached to 100% (10 g/l/48 h) when IolG and IolW were simultaneously overexpressed. The improved conversion was achieved only in the presence of enriched nutrition in the form of 2% (w/v) Bacto soytone in the medium, which may be due to the increasing demand for regeneration of cofactors.
机译:我们之前展示了一种细胞厂的原型,它能够使用与改性肌醇代谢途径的芽孢杆菌枯草芽孢杆菌菌株从肌醇肌醇(MI)转换为Scyllo-inositol(Si)。然而,它浪费了MI的一半,转换率仅限于40-50%。在这项研究中,删除了所有参与MI和Si新陈代谢的“无用”基因,并且在新的菌株中没有浪费MI,尽管达到了SI生产的升高。 IOLG和IOLW是负责转换的关键酶。尝试过表达IOLG和IOLW以转化率进一步升高,当IOLG和IOLW同时过表达时达到100%(10g / L / 48h)的速率。仅在培养基中的2%(w / v)甲酰豆蔻酮的形式的富集营养存在下仅实现改善的转化,这可能是由于对辅助因子的再生需求的增加。

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