Article ID: 2025.09.002
The extracellular export of target chemicals is essential for achieving the target productivity of microbial cell factories (MCFs). We demonstrated that MscCG, a mechanosensitive channel responsible for glutamate export in glutamate-producing MCF of Corynebaterium glutamicum, can export various intracellular low-molecular-weight chemicals outside the cell. The mechanosensitive channels exporter improved L-Lys productivity and conferred substantial 5′-IMP fermentative production ability to the Escherichia coli MCF, which lacks inherent 5′-IMP exporters, indicating that mechanosensitive channels, which are low selective, functioned effectively as MCF exporters. We also demonstrated the effectiveness of a gain-of-function (GOF) mutation of mechanosensitive channels as MCF exporters; however, the essential mechanism underlying this GOF mutation remains unknown. Therefore, we performed molecular dynamics simulations to identify this mechanism at the atomic level. Consequently, we partially elucidated the underlying mechanism of G46D-induced GOF in MscL, which was effective as a 5′-IMP exporter. Specifically, the kink at A38 in the inner transmembrane helix of MscL forming its pore can affect GOF behavior. Based on these results, we conclude that mechanosensitive channels have potential as innovative and versatile exporters of MCFs, capable of enhancing the production efficiency of target chemicals and enabling their production in the absence of natural exporters.
