Mechanosensitive channels are versatile exporters in MCF

The extracellular export of target compounds is essential for achieving the target productivity of microbial cell factories (MCFs). We used a unique patch-clamp system specialized for microorganisms and demonstrated that mechanosensitive channels (Mscs) export various intracellular low-molecular-weight chemical compounds outside the cell. The Msc exporter improved L-Lys productivity and conferred substantial 5′-IMP fermentative production ability to the Escherichia coli MCF, which lacks inherent 5′-IMP exporters. Channels with low selectivity functioned effectively as MCF exporters. We partially elucidated the underlying mechanism of G46D-induced gain of function (GOF) in MscL, unknown for >25 years. Dynamic gating behavior analysis using molecular dynamics (MD) simulations showed that the kink at A38 in the first transmembrane helix of MscL imparts the GOF by affecting the TM1–TM2 contact, inducing conformational changes in TM1 with loss of hydrophobic stable packing in a closed state in the Leu19–Val23 gate region, and enabling easier opening of G46D than in the wild type. Thus, MD simulation can be employed to effectively analyze the dynamic gating behavior of Mscs and improves their function. Mscs are innovative and versatile exporters of MCFs for improving the production efficiency of target compounds and enabling the fermentation of target compounds lacking natural exporters.