Exploring functionality of the reverse β-oxidation pathway in Corynebacterium glutamicum for production of adipic acid
- PMID: 34348702
- PMCID: PMC8336102
- DOI: 10.1186/s12934-021-01647-7
Exploring functionality of the reverse β-oxidation pathway in Corynebacterium glutamicum for production of adipic acid
Abstract
Background: Adipic acid, a six-carbon platform chemical mainly used in nylon production, can be produced via reverse β-oxidation in microbial systems. The advantages posed by Corynebacterium glutamicum as a model cell factory for implementing the pathway include: (1) availability of genetic tools, (2) excretion of succinate and acetate when the TCA cycle becomes overflown, (3) initiation of biosynthesis with succinyl-CoA and acetyl-CoA, and (4) established succinic acid production. Here, we implemented the reverse β-oxidation pathway in C. glutamicum and assessed its functionality for adipic acid biosynthesis.
Results: To obtain a non-decarboxylative condensation product of acetyl-CoA and succinyl-CoA, and to subsequently remove CoA from the condensation product, we introduced heterologous 3-oxoadipyl-CoA thiolase and acyl-CoA thioesterase into C. glutamicum. No 3-oxoadipic acid could be detected in the cultivation broth, possibly due to its endogenous catabolism. To successfully biosynthesize and secrete 3-hydroxyadipic acid, 3-hydroxyadipyl-CoA dehydrogenase was introduced. Addition of 2,3-dehydroadipyl-CoA hydratase led to biosynthesis and excretion of trans-2-hexenedioic acid. Finally, trans-2-enoyl-CoA reductase was inserted to yield 37 µg/L of adipic acid.
Conclusions: In the present study, we engineered the reverse β-oxidation pathway in C. glutamicum and assessed its potential for producing adipic acid from glucose as starting material. The presence of adipic acid, albeit small amount, in the cultivation broth indicated that the synthetic genes were expressed and functional. Moreover, 2,3-dehydroadipyl-CoA hydratase and β-ketoadipyl-CoA thiolase were determined as potential target for further improvement of the pathway.
© 2021. The Author(s).
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
Similar articles
-
Direct biosynthesis of adipic acid from a synthetic pathway in recombinant Escherichia coli.Biotechnol Bioeng. 2014 Dec;111(12):2580-6. doi: 10.1002/bit.25293. Epub 2014 Jul 4. Biotechnol Bioeng. 2014. PMID: 24895214
-
Improved production of adipate with Escherichia coli by reversal of β-oxidation.Appl Microbiol Biotechnol. 2017 Mar;101(6):2371-2382. doi: 10.1007/s00253-016-8033-3. Epub 2016 Dec 8. Appl Microbiol Biotechnol. 2017. PMID: 27933454
-
Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a genome-scale metabolic network model for trans-4-hydroxyproline production.Biotechnol Bioeng. 2019 Jan;116(1):99-109. doi: 10.1002/bit.26818. Epub 2018 Oct 27. Biotechnol Bioeng. 2019. PMID: 30102770
-
[Biosynthesis of adipic acid].Sheng Wu Gong Cheng Xue Bao. 2013 Oct;29(10):1374-85. Sheng Wu Gong Cheng Xue Bao. 2013. PMID: 24432653 Review. Chinese.
-
Strategy for improving L-isoleucine production efficiency in Corynebacterium glutamicum.Appl Microbiol Biotechnol. 2019 Mar;103(5):2101-2111. doi: 10.1007/s00253-019-09632-2. Epub 2019 Jan 20. Appl Microbiol Biotechnol. 2019. PMID: 30663007 Review.
Cited by
-
Microbial cell factories for bio-based biodegradable plastics production.iScience. 2022 Oct 31;25(11):105462. doi: 10.1016/j.isci.2022.105462. eCollection 2022 Nov 18. iScience. 2022. PMID: 36405773 Free PMC article. Review.
-
Reverse β-oxidation pathways for efficient chemical production.J Ind Microbiol Biotechnol. 2022 Apr 14;49(2):kuac003. doi: 10.1093/jimb/kuac003. J Ind Microbiol Biotechnol. 2022. PMID: 35218187 Free PMC article.
References
-
- Rabinovitch-Deere CA, Oliver JWK, Rodriguez GM, Atsumi S. Synthetic biology and metabolic engineering approaches to produce biofuels. Chem Rev. 2013. - PubMed
-
- van Haveren J, Scott EL, Sanders J. Bulk chemicals from biomass. Biofuels Bioprod Biorefining. 2008;2(1):41–57. doi: 10.1002/bbb.43. - DOI
-
- Chen GQ, Patel MK. Plastics derived from biological sources: present and future: a technical and environmental review. Chem Rev. 2012. - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
