Date of Award
1-1-2017
Document Type
Thesis
Degree Name
M.S.
Department
Chemistry and Biochemistry
First Advisor
John A. Latham, Ph.D.
Keywords
Mechanism, Mycofactocin Pathway, Peptide Modification, Radical SAM Enzyme, SPASM Domain
Abstract
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.
Recommended Citation
Khaliullin, Bulat, "Mechanistic Insights into the Radical S-Adenosyl L-Methionine Enzyme MFTC" (2017). Electronic Theses and Dissertations. 1300.
https://digitalcommons.du.edu/etd/1300
Provenance
Received from ProQuest
Rights holder
Bulat Khaliullin
File size
68 p.
Copyright date
2017
File format
application/pdf
Language
en
Discipline
Chemistry, Biochemistry
Comments
Copyright is held by the author.