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bioRxiv · 10.1101/2024.11.04.621991

Systems metabolic engineering of Corynebacterium glutamicum for efficient L-tryptophan production

Dong, Y.·Chen, Z.
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Abstract

Corynebacterium glutamicum is a versatile industrial microorganism for producing various amino acids. However, there have been no reports of well-defined C. glutamicum strains capable of hyperproducing L-tryptophan. This study presents a comprehensive metabolic engineering approach to establish robust C. glutamicum strains for L-tryptophan biosynthesis, including: (1) identification of potential targets by enzyme-constrained genome-scale modeling; (2) enhancement of the L-tryptophan biosynthetic pathway; (3) reconfiguration of central metabolic pathways; (4) identification of metabolic bottlenecks through comparative metabolome analysis; (5) engineering of the transport system, shikimate pathway, and precursor supply; and (6) repression of competing pathways and iterative optimization of key targets. The resulting C. glutamicum strain achieved a remarkable L-tryptophan titer of 50.5 g/L in 48h with a yield of 0.17 g/g glucose in fed-batch fermentation. This study highlights the efficacy of integrating computational modeling with systems metabolic engineering for significantly enhancing the production capabilities of industrial microorganisms.

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Dong, Y., Chen, Z.. 2024-11-05. Systems metabolic engineering of Corynebacterium glutamicum for efficient L-tryptophan production. https://doi.org/10.1101/2024.11.04.621991

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