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MftG is crucial for alcohol metabolism of mycobacteria by linking mycofactocin oxidation to respiration

ABSTRACT: Mycofactocin is a redox cofactor essential for the alcohol metabolism of Mycobacteria. While the biosynthesis of mycofactocin is well established, the mftG gene, which encodes an oxidoreductase of the glucose-methanol-choline superfamily remained functionally uncharacterized. Here, we show that MftG enzymes strictly require mft biosynthetic genes, and are found in 75% of organisms harboring these genes. Gene deletion experiments in Mycolicibacterium smegmatis demonstrated a growth defect of the ∆mftG mutant on ethanol as a carbon source, accompanied by an arrest of cell division reminiscent of mild starvation. Investigation of carbon and cofactor metabolism implied a defect in mycofactocin re-oxidation. Cell-free enzyme assays and respirometry using isolated cell membranes indicated that MftG acts as a mycofactocin dehydrogenase shuttling electrons toward the respiratory chain. Transcriptomics studies also indicated remodeling of redox metabolism to compensate for a shortage of redox equivalents. In conclusion, this work closes an important knowledge gap concerning the mycofactocin system and adds a new pathway to the intricate web of redox reactions governing the metabolism of mycobacteria.

ORGANISM(S): Mycolicibacterium smegmatis MC2 155

PROVIDER: GSE250373 | GEO | 2024/03/01

REPOSITORIES: GEO

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