Mycofactocin

Mycofactocin is a ribosomally synthesized and post-translationally modified peptide, or RiPP. It was discovered in a bioinformatics study in 2011.^[1] Its biosynthesis depends on the mycofactocin precursor binding protein MftB and the radical SAM enzyme MftC,^[2][3] and may require additional steps that are not yet characterized. The mycofactocin biosynthesis pathway is one of the most abundant of any RiPP system in the collection of bacterial genomes sequenced to date, with a species distribution heavily skewed towards the Actinobacteria, including Mycobacterium tuberculosis, which is the causative agent of tuberculosis and therefore the number one killer among bacterial pathogens of humans.

The name "mycofactocin" is derived from three words, the genus name Mycobacterium (across which it is nearly universal), cofactor because its presence in a genome predicts the co-occurrence of certain families of enzymes as if it is a cofactor they require, and bacteriocin because biosynthesis of subtilosin A, a bacteriocin, relies on a related radical SAM enzyme. Mycofactocin is thought to play a role in redox pathways involving nicotinoproteins, enzymes with non-exchangeable bound nicotinamide adenine dinucleotide (NAD). This notion comes largely from comparative genomics work that highlighted the many parallels between mycofactocin and pyrroloquinoline quinone (PQQ).^[4] In both cases, maturation of the RiPP requires modification of a tyrosine residue by a radical SAM enzyme, the system appears in very similar form in large numbers of species, the product appears not be exported, and several families of enzymes occur exclusively in bacteria with those systems. The number of putatively mycofactocin-dependent oxidoreductases encoded by a single genome can be quite large: at least 19 for Rhodococcus jostii RHA1, and 26 for the short chain dehydrogenase/reductase (SDR) alone in Mycobacterium avium.

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