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000894472 1001_ $$0P:(DE-Juel1)176186$$aRamp, Paul$$b0
000894472 245__ $$aMetabolic engineering of Corynebacterium glutamicum for production of scyllo-inositol, a drug candidate against Alzheimer's disease
000894472 260__ $$aOrlando, Fla.$$bAcademic Press$$c2021
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000894472 520__ $$aScyllo-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.
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000894472 7001_ $$0P:(DE-Juel1)180545$$aLehnert, Alexander$$b1
000894472 7001_ $$0P:(DE-Juel1)165848$$aMatamouros, Susana$$b2
000894472 7001_ $$0P:(DE-Juel1)171825$$aWirtz, Astrid$$b3
000894472 7001_ $$0P:(DE-Juel1)145489$$aBaumgart, Meike$$b4
000894472 7001_ $$0P:(DE-Juel1)128943$$aBott, Michael$$b5$$eCorresponding author
000894472 773__ $$0PERI:(DE-600)1471017-1$$a10.1016/j.ymben.2021.06.011$$gVol. 67, p. 173 - 185$$p173 - 185$$tMetabolic engineering$$v67$$x1096-7176$$y2021
000894472 8564_ $$uhttps://juser.fz-juelich.de/record/894472/files/Ramp%20et%20al%202021%20R1.pdf$$yPublished on 2021-09-01. Available in OpenAccess from 2022-09-01.$$zStatID:(DE-HGF)0510
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