Researcher(s)
- Jeremiah Epting, Biochemistry, University of Delaware
Faculty Mentor(s)
- Catherine Grimes, Chemistry and Biochemistry, University of Delaware
Abstract
The bacteria cell wall is surrounded by peptidoglycan (PG), which helps protect the bacteria from external factors and provides structural support to the cell wall. The basic structure of the bacterial PG is made from the polymerization of the carbohydrate subunits N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG), with a peptide chain of alternating L- and D- amino acids extending from the NAM unit, that is then further crosslinked to other growing polymer chains of NAM and NAG. Fragments of PG, specifically NAM, shed from the bacteria and are recycled to conserve resources vital for growth, or as a means to avoid targeting by antibiotics or detection from host immune systems. Bioorthogonal NAM derivatives, containing chemical groups that do not affect native biochemical properties, were developed by the Grimes lab as a means of labeling bacteria by hijacking their recycling capabilities further providing ways to study its structure and biosynthesis. Currently, NAM probes contain the bioorthogonal handle on the 2-position, however, some bacteria are known to be able to modify that position during their PG biosynthesis. Evaluating and expanding NAM probes to other positions is crucial for improved biological incorporation of these probes. NAM probes with labeling stemming from the 3-position have been synthesized in the Grimes lab, however, their limitations needed further investigation to gauge how they can be integrated into biological analysis. Exploring the 3-position of NAM and understanding its limits is vital for the development of our NAM library. By diversifying the NAM probe catalog and creating NAM probes that utilize other positions on NAM, biochemical evaluations will be expanded to wider scopes of bacterial species, such as mycobacterium tuberculosis. This newer generation of NAM probes will prove useful for the microbial community to further understand bacterial structures and biosynthesis in attempts to combat these deadly bacterial infections.