title: Catalytic control of enzymatic fluorine specificity.
abstract: The investigation of unique chemical phenotypes has led to the discovery of enzymes with interesting behaviors that allow us to explore unusual function. The organofluorine-producing microbe Streptomyces cattleya has evolved a fluoroacetyl-CoA thioesterase (FlK) that demonstrates a surprisingly high level of discrimination for a single fluorine substituent on its substrate compared with the cellularly abundant hydrogen analog, acetyl-CoA. In this report, we show that the high selectivity of FlK is achieved through catalysis rather than molecular recognition, where deprotonation at the C(α) position to form a putative ketene intermediate only occurs on the fluorinated substrate, thereby accelerating the rate of hydrolysis 10(4)-fold compared with the nonfluorinated congener. These studies provide insight into mechanisms of catalytic selectivity in a native system where the existence of two reaction pathways determines substrate rather than product selection.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Weeks
authors.forename: Michelle C Y
authors.initials: MC
authors.lastname: Chang
mesh_terms: D002384:Catalysis; D005461:Fluorine / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics
chemical_list: D005461:Fluorine