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Catalytic control of enzymatic fluorine specificity
- Weeks, Amy M., Chang, Michelle C. Y.
- Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.48 pp. 19667-19672
- Streptomyces cattleya, acetyl coenzyme A, catalytic activity, enzymes, fluorine, hydrogen, hydrolysis, phenotype
- 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.