Synthetic redesign of Corynebacterium glutamicum for 1,4-butanediol production via L-glutamate-derived CoA-independent pathway

1,4-Butanediol (1,4-BDO) is a key commodity chemical used in the production of various products, including plastics, fibers, and polyesters. Here, a potent microbial platform for 1,4-BDO production from glucose via the L-glutamate-derived CoA-independent pathway was developed using Corynebacterium glutamicum as the host strain. Introducing a CoA-independent 1,4-BDO biosynthesis pathway and removing a metabolic flux bypass, the resulting initial strain produced 2.20 g/L of 1,4-BDO from glucose. Upon prolonged cultivation, C. glutamicum showed an endogenous capacity to degrade 1,4-BDO. Transcriptomic analysis was conducted to identify genes potentially involved in this pathway. Among them, fadH, aldH, and adhA were verified as the key enzymes for 1,4-BDO degradation. The deletion of three dehydrogenase genes from the initial strain removed the product degradation and achieved an improved 1,4-BDO titer of 3.14 g/L. Finally, fed-batch fermentation of the final strain was conducted, resulting in 13.4 g/L of 1,4-BDO production. This work demonstrates the first successful development of C. glutamicum as a potent platform strain for the biosynthesis of 1,4-BDO.