Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis

Prell C, Burgardt A, Meyer F, Wendisch VF (2021)
Frontiers in Bioengineering and Biotechnology 8: 630476.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
L-2-hydroxyglutarate (L-2HG) is a trifunctional building block and highly attractive for the chemical and pharmaceutical industries. The natural L-lysine biosynthesis pathway of the amino acid producer Corynebacterium glutamicum was extended for the fermentative production of L-2HG. Since L-2HG is not native to the metabolism of C. glutamicum metabolic engineering of a genome-streamlined L-lysine overproducing strain was required to enable the conversion of L-lysine to L-2HG in a six-step synthetic pathway. To this end, L-lysine decarboxylase was cascaded with two transamination reactions, two NAD(P)-dependent oxidation reactions and the terminal 2-oxoglutarate-dependent glutarate hydroxylase. Of three sources for glutarate hydroxylase the metalloenzyme CsiD from Pseudomonas putida supported L-2HG production to the highest titers. Genetic experiments suggested a role of succinate exporter SucE for export of L-2HG and improving expression of its gene by chromosomal exchange of its native promoter improved L-2HG production. The availability of Fe2+ as cofactor of CsiD was identified as a major bottleneck in the conversion of glutarate to L-2HG. As consequence of strain engineering and media adaptation product titers of 34 ± 0 mM were obtained in a microcultivation system. The glucose-based process was stable in 2 L bioreactor cultivations and a L-2HG titer of 3.5 g L−1 was obtained at the higher of two tested aeration levels. Production of L-2HG from a sidestream of the starch industry as renewable substrate was demonstrated. To the best of our knowledge, this study is the first description of fermentative production of L-2HG, a monomeric precursor used in electrochromic polyamides, to cross-link polyamides or to increase their biodegradability.
Erscheinungsjahr
2021
Zeitschriftentitel
Frontiers in Bioengineering and Biotechnology
Band
8
Art.-Nr.
630476
eISSN
2296-4185
Page URI
https://pub.uni-bielefeld.de/record/2949664

Zitieren

Prell C, Burgardt A, Meyer F, Wendisch VF. Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis. Frontiers in Bioengineering and Biotechnology. 2021;8: 630476.
Prell, C., Burgardt, A., Meyer, F., & Wendisch, V. F. (2021). Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis. Frontiers in Bioengineering and Biotechnology, 8, 630476. https://doi.org/10.3389/fbioe.2020.630476
Prell, C., Burgardt, A., Meyer, F., and Wendisch, V. F. (2021). Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis. Frontiers in Bioengineering and Biotechnology 8:630476.
Prell, C., et al., 2021. Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis. Frontiers in Bioengineering and Biotechnology, 8: 630476.
C. Prell, et al., “Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis”, Frontiers in Bioengineering and Biotechnology, vol. 8, 2021, : 630476.
Prell, C., Burgardt, A., Meyer, F., Wendisch, V.F.: Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis. Frontiers in Bioengineering and Biotechnology. 8, : 630476 (2021).
Prell, Carina, Burgardt, Arthur, Meyer, Florian, and Wendisch, Volker F. “Fermentative production of ʟ-2-hydroxyglutarate by engineered Corynebacterium glutamicum via pathway extension of ʟ-lysine biosynthesis”. Frontiers in Bioengineering and Biotechnology 8 (2021): 630476.
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