Scyllo-inositol has been identified as a potential drug for the treatment of Alzheimer's disease. Therefore, cost-efficient processes for the production of this compound are desirable. In this study, we analyzed and engineered Corynebacterium glutamicum with the aim to develop competitive scyllo-inositol producer strains. Initial studies revealed that C. glutamicum naturally produces scyllo-inositol when cultured with myo-inositol as carbon source. The conversion involves NAD⁺-dependent oxidation of myo-inositol to 2-keto-myo-inositol followed by NADPH-dependent reduction to scyllo-inositol. Use of myo-inositol for biomass formation was prevented by deletion of a cluster of 16 genes involved in myo-inositol catabolism (strain MB001(DE3)Δiol1). Deletion of a second cluster of four genes (oxiC-cg3390-oxiD-oxiE) related to inositol metabolism prevented conversion of 2-keto-myo-inositol to undesired products causing brown coloration (strain MB001(DE3)Δiol1Δiol2). The two chassis strains were used for plasmid-based overproduction of myo-inositol dehydrogenase (IolG) and scyllo-inositol dehydrogenase (IolW). In BHI medium containing glucose and myo-inositol, a complete conversion of the consumed myo-inositol into scyllo-inositol was achieved with the Δiol1Δiol2 strain. To enable scyllo-inositol production from cheap carbon sources, myo-inositol 1-phosphate synthase (Ino1) and myo-inositol 1-phosphatase (ImpA), which convert glucose 6-phosphate into myo-inositol, were overproduced in addition to IolG and IolW using plasmid pSI. Strain MB001(DE3)Δiol1Δiol2 (pSI) produced 1.8 g/L scyllo-inositol from 20 g/L glucose and even 4.4 g/L scyllo-inositol from 20 g/L sucrose within 72 h. Our results demonstrate that C. glutamicum is an attractive host for the biotechnological production of scyllo-inositol and potentially further myo-inositol-derived products.

鲨肌醇已被确定为治疗阿尔茨海默病的潜在药物。因此，需要具有成本效益的生产这种化合物的方法。在这项研究中，我们分析并改造了谷氨酸棒杆菌，旨在开发具有竞争力的鲨肌醇生产菌株。初始研究表明，谷氨酸棒杆菌天然产生鲨当与培养肌醇肌醇肌醇作为碳源。所述转换涉及NAD ⁺的依赖性氧化肌肉肌醇向2-酮肌肉肌醇随后NADPH依赖性降低到鲨-肌醇。的使用肌肉被阻止的16个基因参与了簇的缺失肌醇用于生物质形成肌醇肌醇代谢（菌株MB001（DE3）Δ IOL1）。删除与肌醇代谢相关的第二组四个基因 ( oxiC - cg3390 -oxiD-oxiE ) 阻止了 2-酮-肌醇转化为不想要的产物，导致棕色着色（菌株 MB001(DE3)Δ iol1 Δ iol2）。两个机箱株用于的基于质粒的生产过剩肌肌醇脱氢酶（IolG）和鲨肌醇脱氢酶（IolW）。在含有葡萄糖和肌钙蛋白的BHI 培养基中-肌醇，使用 Δ iol1 Δ iol2菌株实现了消耗的肌醇完全转化为鲨肌醇。为了使鲨从廉价的碳源肌醇产生，肌醇-1-磷酸合酶（INO1）和肌醇肌醇-1-磷酸酶（IMPA），其将葡萄糖转化-6-磷酸转化为肌醇肌醇，被除过量产生到IolG和IolW 使用质粒 pSI。菌株 MB001(DE3)Δ iol1 Δ iol2 ( pSI )从 20 g/L 葡萄糖产生 1.8 g/L鲨肌醇，甚至 4.4 g/L鲨肌醇- 72 小时内从 20 g/L 蔗糖中提取肌醇。我们的研究结果表明，谷氨酸棒状杆菌是用于生物技术生产的有吸引力的宿主鲨肌醇和可能进一步肌醇肌醇衍生的产物。