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

Corynebacterium glutamicum is a versatile industrial microorganism for producing various amino acids. However, there have been no reports of a well-defined C. glutamicum strain capable of hyperproducing L-tryptophan. This study presents a comprehensive metabolic engineering approach to establish a robust C. glutamicum cell factory for L-tryptophan biosynthesis, including: (1) identification of potential targets using an enzyme-constrained genome-scale model; (2) targeted 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 engineered C. glutamicum strain achieved a remarkable L-tryptophan titer of 16.2 g/L with a yield of 0.16 g/g glucose in shake-flask fermentation. This study highlights the efficacy of integrating computational modeling with systems metabolic engineering for significantly enhancing the production capabilities of industrial microorganisms.