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Mediating oxidative stress enhances α-ionone biosynthesis and strain robustness during process scaling up.
- Source :
-
Microbial cell factories [Microb Cell Fact] 2022 Nov 23; Vol. 21 (1), pp. 246. Date of Electronic Publication: 2022 Nov 23. - Publication Year :
- 2022
-
Abstract
- Background: α-Ionone is highly valued in cosmetics and perfumery with a global usage of 100-1000 tons per year. Metabolic engineering by microbial fermentation offers a promising way to produce natural (R)-α-ionone in a cost-effective manner. Apart from optimizing the metabolic pathways, the approach is also highly dependent on generating a robust strain which retains productivity during the scale-up process. To our knowledge, no study has investigated strain robustness while increasing α-ionone yield.<br />Results: Built on our previous work, here, we further increased α-ionone yield to 11.4 mg/L/OD in 1 mL tubes by overexpressing the bottleneck dioxygenase CCD1 and re-engineering the pathway, which is > 65% enhancement as compared to our previously best strain. However, the yield decreased greatly to 2.4 mg/L/OD when tested in 10 mL flasks. Further investigation uncovered an unexpected inhibition that excessive overexpression of CCD1 was accompanied with increased hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ) production. Excessive H <subscript>2</subscript> O <subscript>2</subscript> broke down lycopene, the precursor to α-ionone, leading to the decrease in α-ionone production in flasks. This proved that expressing too much CCD1 can lead to reduced production of α-ionone, despite CCD1 being the rate-limiting enzyme. Overexpressing the alkyl hydroperoxide reductase (ahpC/F) partially solved this issue and improved α-ionone yield to 5.0 mg/L/OD in flasks by reducing oxidative stress from H <subscript>2</subscript> O <subscript>2</subscript> . The strain exhibited improved robustness and produced ~ 700 mg/L in 5L bioreactors, the highest titer reported in the literature.<br />Conclusion: Our study provides an insight on the importance of mediating the oxidative stress to improve strain robustness and microbial production of α-ionone during scaling up. This new strategy may be inspiring to the biosynthesis of other high-value apocarotenoids such as retinol and crocin, in which oxygenases are also involved.<br /> (© 2022. The Author(s).)
- Subjects :
- Metabolic Engineering
Oxidative Stress
Hydrogen Peroxide
Norisoprenoids metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2859
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Microbial cell factories
- Publication Type :
- Academic Journal
- Accession number :
- 36424649
- Full Text :
- https://doi.org/10.1186/s12934-022-01968-1