2015 Beckman Symposium   

Hannah Martin

Presentation Date:
August-6-2015

Presenter:
Hannah Martin

Title:
The Biosynthesis of the Molybdenum Cofactor in Bacillus subtilis

Institution:
Wake Forest University

Department:
Chemistry

Description:
Molybdenum (Mo), an essential trace element in the majority of living organisms, gains biological activity when complexed to a protein cofactor (Moco). The absence of functional Moco causes a myriad of metabolic dysfunctions. In humans, the absence of Moco leads to the toxic accumulation of sulfite in the brain due to a lack of sulfite oxidase, a Moco-containing enzyme. Moco deficiency manifests soon after birth and is ultimately fatal. Although the biosynthetic pathway for Moco has been elucidated in humans, plants, and Gram-negative bacteria, it remains unresolved in Gram-positive bacteria. For active Moco to be synthesized, two sulfur atoms must be inserted into the organic pterin scaffold. In the Gram-negative bacteria Escherichia coli, both sulfur atoms are mobilized from the free amino acid cysteine via the cysteine desulfurase IscS and subsequently transferred into the scaffold by a series of reactions involving five additional proteins (TusA, YnjE, MoaE, MoaD, and MoeB). Most Gram-positive bacteria lack IscS, TusA and YnjE, suggesting this subgroup of microbes uses a distinct strategy for sulfur activation and insertion. This project aims to identify the route of sulfur transfer in Moco biogenesis in the model Gram-positive bacterium Bacillus subtilis. Using a combination of phenotypic, biochemical, and bioanalytical approaches, we investigated the involvement of the candidate sulfur transfer protein YrkF, which displays similarity to TusA, and the four cysteine desulfurases YrvO, NifS, NifZ, SufS. Ultimately, this project seeks to contribute to current understanding of both divergent biosynthetic pathways and sulfur mobilization in Gram-positive bacteria, with the potential for novel drug targets.


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