Date of Award
Chemistry and Biochemistry
John A. Latham
Schuyler van Engelenburg
mechanism, mycofactocin pathway, peptide modification, radical SAM enzyme, SPASM domain
Mycofactocin is a putative peptide-derived redox cofactor in Mycobacterium family. Its putative biosynthetic pathway is encoded by the operon mftABCDEF. The initial step of this pathway is a posttranslational modification of a peptide precursor MftA, which is catalyzed by MftC enzyme. This modification only occurs in the presence of chaperone MftB. Here, we demonstrate that MftC is a radical S-adenosyl L-methionine (SAM) enzyme and we examine its catalytic mechanism. We show that the modification of MftA requires two equivalents of SAM and is implemented in two steps: (i) the decarboxylation of a C-terminal tyrosine, resulting in formation of an intermediate with a carbon-carbon double bond, and (ii) the cross-linking of the tyrosine with the penultimate valine, leading to formation of a cyclized product. We also show that MftC is able to modify unnatural peptide substrates, resulting in formation of specific and non-specific products.
Khaliullin, Bulat, "Mechanistic Insights into the Radical S-Adenosyl L-Methionine Enzyme MFTC" (2017). Electronic Theses and Dissertations. 1300.
Recieved from ProQuest