Multiomics Analysis Provides Insight into the Laboratory Evolution of toward the Metabolic Usage of Fluorinated Indoles.

Organofluorine compounds are known to be toxic to a broad variety of living beings in different habitats, and chemical fluorination has been historically exploited by mankind for the development of therapeutic drugs or agricultural pesticides. On the other hand, several studies so far have demonstrated that, under appropriate conditions, living systems (in particular bacteria) can tolerate the presence of fluorinated molecules (e.g.

Deciphering the Fluorine Code-The Many Hats Fluorine Wears in a Protein Environment.

Deciphering the fluorine code is how we describe not only the focus of this Account, but also the systematic approach to studying the impact of fluorine's incorporation on the properties of peptides and proteins used by our groups and others. The introduction of fluorine has been shown to impart favorable, but seldom predictable, properties to peptides and proteins, but up until about two decades ago the outcomes of fluorine modification of peptides and proteins were largely left to chance. Driven by the motivation to extend the application of the unique properties of the element fluorine from medicinal and agro chemistry to peptide and protein engineering we have established extensive research programs that enable the systematic investigation of effects that accompany the introduction of fluorine into this class of biopolymers.

Fluorine teams up with water to restore inhibitor activity to mutant BPTI.

Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C-F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site.

Chemical aminoacylation of tRNAs with fluorinated amino acids for in vitro protein mutagenesis.

This article describes the chemical aminoacylation of the yeast phenylalanine suppressor tRNA with a series of amino acids bearing fluorinated side chains via the hybrid dinucleotide pdCpA and ligation to the corresponding truncated tRNA species. Aminoacyl-tRNAs can be used to synthesize biologically relevant proteins which contain fluorinated amino acids at specific sites by means of a cell-free translation system. Such engineered proteins are expected to contribute to our understanding of discrete fluorines' interaction with canonical amino acids in a native protein environment and to enable the design of fluorinated proteins with arbitrary desired properties.