Optogenetic Programming of L-Lysine Production in Corynebacterium glutamicum : A Green Alternative to Chemical Induction
Corynebacterium glutamicum is a cornerstone microbial chassis for industrial amino acid production, yet metabolic engineering in this organism still relies on static gene expression strategies that lack temporal flexibility and impose metabolic burden. Optogenetics offers a non-invasive and reversible alternative for dynamically coordinating cellular processes, but its application in C. glutamicum remains limited. Here, we establish an EL222-based, one-component optogenetic system enabling bidirectional, dynamic transcriptional control in C. glutamicum. By mitigating EL222-associated phototoxicity and optimizing illumination parameters, we developed blue light-induced and blue light-repressed expression modules with tunable responses. Applying these tools to L-lysine biosynthesis allowed light-responsive regulation of key pathway genes. In shake-flask batch fermentation, strain CG62 produced 2.96 ± 0.11 g L–1 L-lysine under blue light after 60 h, compared with 1.47 ± 0.12 g L–1 in the dark, representing a 101.36% increase in L-lysine titer. We establish a comparatively simple one-component EL222-based framework that supports both blue light-induced and blue light-repressed transcriptional regulation in C. glutamicum and demonstrate its application to dynamic control of L-lysine biosynthesis. This work expands the optogenetic toolkit for C. glutamicum and highlights light-driven dynamic regulation as a versatile strategy for optimizing industrial microbial cell factories.