Lysine production from the sugar alcohol mannitol: Design of the cell factory Corynebacterium glutamicum SEA-3 through integrated analysis and engineering of metabolic pathway fluxes - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Metabolic Engineering Année : 2018

Lysine production from the sugar alcohol mannitol: Design of the cell factory Corynebacterium glutamicum SEA-3 through integrated analysis and engineering of metabolic pathway fluxes

Résumé

The amino acid lysine is among the world’s most important biotechnological products, and enabling its manufacture from the most attractive new materials is an ever-present challenge. In this study, we describe a cell factory of Corynebacterium glutamicum, which produces lysine from mannitol. A preliminary mutant obtained by the deletion of the mannitol repressor MtlR in the glucose-based, lysine-producing C. glutamicum produced only small amounts of lysine. This limitation was due to the significant accumulation of fructose and a limited NADPH supply, which caused a low flux of only 6% into the oxidative pentose phosphate (PP) pathway. Subsequent expression of fructokinase slightly increased production but failed to substantially redirect the flux from the Emden-Meyerhof-Parnas (EMP) pathway to the PP pathway. This suggested the design C. glutamicum SEA-3, which overexpressed the NADPH-dependent glyceraldehyde 3-phosphate dehydrogenase GapN from Streptococcus mutans and coupled the EMP pathway flux to NADPH formation. When grown on mannitol, the SEA-3 strain had a lysine yield of 0.24 mol mol-1 and a specific productivity of 1.1 mmol g-1 h-1, approximately 50% and 70% higher, respectively, than those of the basic producer. A computational pathway analysis revealed that this design would potentially enable a lysine yield of 0.9 mol mol-1, providing room for further development. Our findings open new avenues for lysine production from marine macroalgae, which is farmed globally as an attractive third-generation renewable resource. Mannitol is a major constituent of these algae (up to 30% and higher) and can be easily extracted from their biomass with hot water.
Fichier principal
Vignette du fichier
Hoffmann-ME-2018-manuscript-LISBP_1.pdf (1.65 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01886463 , version 1 (26-05-2020)

Identifiants

Citer

Sarah Lisa Hoffmann, Lukas Jungmann, Sarah Schiefelbein, Lindsay Peyriga, Edern Cahoreau, et al.. Lysine production from the sugar alcohol mannitol: Design of the cell factory Corynebacterium glutamicum SEA-3 through integrated analysis and engineering of metabolic pathway fluxes. Metabolic Engineering, 2018, ⟨10.1016/j.ymben.2018.04.019⟩. ⟨hal-01886463⟩
105 Consultations
258 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More