This title appears in the Scientific Report :
2021
Please use the identifier:
http://hdl.handle.net/2128/28582 in citations.
Please use the identifier: http://dx.doi.org/10.1016/j.ymben.2021.06.011 in citations.
Metabolic engineering of Corynebacterium glutamicum for production of scyllo-inositol, a drug candidate against Alzheimer's disease
Metabolic engineering of Corynebacterium glutamicum for production of scyllo-inositol, a drug candidate against Alzheimer's disease
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 scyll...
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Personal Name(s): | Ramp, Paul |
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Lehnert, Alexander / Matamouros, Susana / Wirtz, Astrid / Baumgart, Meike / Bott, Michael (Corresponding author) | |
Contributing Institute: |
Biotechnologie; IBG-1 |
Published in: | Metabolic engineering, 67 (2021) S. 173 - 185 |
Imprint: |
Orlando, Fla.
Academic Press
2021
|
PubMed ID: |
34224896 |
DOI: |
10.1016/j.ymben.2021.06.011 |
Document Type: |
Journal Article |
Research Program: |
Utilization of renewable carbon and energy sources and engineering of ecosystem functions |
Link: |
Published on 2021-09-01. Available in OpenAccess from 2022-09-01. |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1016/j.ymben.2021.06.011 in citations.
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. |