Catalytic control of enzymatic fluorine specificity

Amy M. Weeks, Michelle C.Y. Chang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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 Cα position to form a putative ketene intermediate only occurs on the fluorinated substrate, thereby accelerating the rate of hydrolysis 104-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.

Original languageEnglish (US)
Pages (from-to)19667-19672
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number48
StatePublished - Nov 27 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


  • Enzyme mechanism
  • Substrate selectivity


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