Identification and expression of small multidrug resistance transporters in early-branching anaerobic fungi

Membrane-embedded transporters impart essential functions to cells as they mediate sensing and the uptake and extrusion of nutrients, waste products, and effector molecules. Promiscuous multidrug exporters are implicated in resistance to drugs and antibiotics and are highly relevant for microbial engineers who seek to enhance the tolerance of cell factory strains to hydrophobic bioproducts. Here, we report on the identification of small multidrug resistance (SMR) transporters in early-branching anaerobic fungi (Neocallimastigomycetes). The SMR class of transporters is commonly found in bacteria but has not previously been reported in eukaryotes. In this study, we show that SMR transporters from anaerobic fungi can be produced heterologously in the model yeast Saccharomyces cerevisiae, demonstrating the potential of these proteins as targets for further characterization. The discovery of these novel anaerobic fungal SMR transporters offers a promising path forward to enhance bioproduction from engineered microbial strains.

Automated summary

Membrane-embedded transporters play essential roles in cellular functions such as nutrient uptake and waste product extrusion. Multidrug exporters are important for resistance mechanisms and enhancing tolerance to hydrophobic bioproducts in microbial engineering. In this study, we identified small multidrug resistance (SMR) transporters in anaerobic fungi, which have not been reported in eukaryotes before. We demonstrated the potential of these SMR transporters as targets for further characterization by heterologously producing them in the yeast Saccharomyces cerevisiae. These novel anaerobic fungal SMR transporters offer a promising approach to enhance bioproduction in engineered microbial strains.