Elucidating the mutation-induced conformational changes in hexose transporter for co-utilization of glucose and...

Efficient co-utilization of glucose and xylose by Saccharomyces cerevisiae is crucial for economical biofuel production from renewable feedstocks. The F79S mutation in the hexose transporter HXT7 enhances xylose uptake, but the underlying molecular mechanism remains elusive. We employ molecular dynamics simulations to elucidate the conformational changes induced by the F79S mutation and xylose binding. The xylose-bound mutant exhibited higher structural deviation than the wild-type. Additionally, key flexible regions were identified, particularly in the inner region of the xylose-bound mutant, suggesting areas crucial for enhanced transport. Principal Component Analysis unveils a diverse conformational landscape in xylose-bound systems, indicating enhanced dynamic behaviour facilitating substrate transport. Moreover, the mutation-induced conformational changes in xylose-bound and unbound HXT7 were analysed by protein structure network. A reduction in transmembrane hub residues from 21 to 16 in the xylose-bound mutant suggested increased flexibility in the transport channel. Notably, we identified five key aromatic hub residues (81W, 122F, 153Y, 208Y, and 492F) in the transmembrane channel, which might be targeted for further improvement of xylose transport. These molecular insights provide a mechanistic basis for the enhanced xylose transport by the F79S mutant and offer new targets for rational engineering of transporters, paving the way for improved lignocellulosic biomass utilization in industrial applications.