Undergraduate Research & Scholarships

Nicholas Lue Rose Hills

Kinetic Analysis of the Fluorine-Specific Thioesterase FlK

FlK is an enzyme found in the soil bacterium Streptomyces cattleya, in which it confers resistance to the toxic metabolite fluoroacetate by breaking down its activated form, fluoroacetyl-CoA. Interestingly, FlK has evolved to discriminate between fluoroacetyl-CoA and its nonfluorinated analogue, the metabolically crucial acetyl-CoA, displaying a million-fold higher catalytic efficiency for the former. Although previous work has elucidated some of the mechanisms of fluorine specificity in FlK, the role of the arginine residue at site 120 (Arg120) has not yet been explored. Recent research suggests that Arg120s positively charged side chain is positioned in FlKs active site close to the substrate fluorine atom, and therefore may be involved in correctly positioning fluoroacetyl-CoA for catalysis by stabilizing the fluorine. I will carry out Michaelis-Menten and pre-steady-state kinetic analyses of both wild-type FlK- and mutant FlK-catalyzed reactions in order to investigate the function of Arg120. This knowledge will enrich our understanding of enzymatic fluorine specificity, ultimately aiding efforts to engineer enzymes to selectively incorporate fluorine into biosynthetic molecules.

Message To Sponsor

Thank you so much for giving me this invaluable opportunity to devote myself full-time to research. The funding and support that the Rose Hills Foundation has provided are resources that will allow me to develop as a researcher and continue on my path toward a career as a scientist. This summer, I will be able to apply the chemistry I have learned in order to contribute to our understanding of this peculiar enzyme, along the way becoming more independent in my research. I am grateful for this chance to not only get excited about FlK, but get as excited about it as possible!
Profile image of Nicholas Lue
Major: Chemical Biology
Mentor: Michelle Chang, Chemistry
Sponsor: Rose Hills
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