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| Hauptseite > Publikationsdatenbank > Alternative routes for production of the drug candidate d-chiro-inositol with Corynebacterium glutamicum using endogenous or promiscuous plant enzymes > print |
| Hauptseite > Publikationsdatenbank > Alternative routes for production of the drug candidate d-chiro-inositol with Corynebacterium glutamicum using endogenous or promiscuous plant enzymes > print |
| 001 | 1007355 | ||
| 005 | 20231027114403.0 | ||
| 024 | 7 | _ | |a 10.1016/j.ymben.2023.04.013 |2 doi |
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| 100 | 1 | _ | |a Ramp, Paul |0 P:(DE-Juel1)176186 |b 0 |u fzj |
| 245 | _ | _ | |a Alternative routes for production of the drug candidate d-chiro-inositol with Corynebacterium glutamicum using endogenous or promiscuous plant enzymes |
| 260 | _ | _ | |a Orlando, Fla. |c 2023 |b Academic Press |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a d-chiro-Inositol (DCI) is a promising drug candidate for treating insulin resistance and associated diseases such as type 2 diabetes or polycystic ovary syndrome. In this study, we developed two production processes for DCI using Corynebacterium glutamicum as host. In the first process, myo-inositol (MI) is oxidized to 2-keto-myo-inositol (2KMI) by the inositol dehydrogenase (IDH) IolG and then isomerized to 1-keto-d-chiro-inositol (1KDCI) by the isomerases Cg0212 or Cg2312, both of which were identified in this work. 1KDCI is then reduced to DCI by IolG. Overproduction of IolG and Cg0212 in a chassis strain unable to degrade inositols allowed the production of 1.1 g/L DCI from 10 g/L MI. As both reactions involved are reversible, only a partial conversion of MI to DCI can be achieved. To enable higher conversion ratios, a novel route towards DCI was established by utilizing the promiscuous activity of two plant-derived enzymes, the NAD+-dependent d-ononitol dehydrogenase MtOEPa and the NADPH-dependent d-pinitol dehydrogenase MtOEPb from Medicago truncatula (barrelclover). Heterologous production of these enzymes in the chassis strain led to the production of 1.6 g/L DCI from 10 g/L MI. For replacing the substrate MI by glucose, the two plant genes were co-expressed with the endogenous myo-inositol-1-phosphate synthase gene ino1 either as a synthetic operon or using a novel, bicistronic T7-based expression vector. With the single operon construct, 0.75 g/L DCI was formed from 20 g/L glucose, whereas with the bicistronic construct 1.2 g/L DCI was obtained, disclosing C. glutamicum as an attractive host for of d-chiro-inositol production. |
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| 700 | 1 | _ | |a Bott, Michael |0 P:(DE-Juel1)128943 |b 3 |
| 773 | _ | _ | |a 10.1016/j.ymben.2023.04.013 |g Vol. 78, p. 1 - 10 |0 PERI:(DE-600)1471017-1 |p 1 - 10 |t Metabolic engineering |v 78 |y 2023 |x 1096-7176 |
| 856 | 4 | _ | |y Published on 2023-05-03. Available in OpenAccess from 2024-05-03. |u https://juser.fz-juelich.de/record/1007355/files/Postprint%20Ramp%20et%20al%202023%20R1%20with%20figures.pdf |
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