2 Nov 2017
In the design of synthetic molecules, fluorine is an important element to industries as diverse as pharmaceuticals, agriculture, and materials. Teflon coatings for cooking pans and water-repellent Gore-Tex jackets are both based on polytetrafluoroethylene, around 30% of agrichemical compounds contain fluorine, and drugs such as antimalarials, inhalation anesthetics, blood subsitutes and liquid ventilation agents also benefit.
But although a range of industries use it, natural organic compounds that contain fluorine are rare, as very few living organisms produce it. In a recent study, chemists at the University of California, Berkley, US, have found a way to genetically engineer a microbial host for organofluorine metabolism, allowing it to produce a fluoridated intermediate known as diketide.
Given the potential for living systems to produce highly complex chemical compounds, researchers working with Michelle CY Chang at UC, Berkeley aimed to manipulate the biosynthetic machinery in cells to use simple fluorinated building blocks to make new organofluorine target molecules.
To achieve this, they introduced genes that code for three particularly efficient enzymes from a variety of other microorganisms into the bacterium, Escherichia coli, to construct the diketide biosynthesis pathway. These enzymes use fluorine-containing derivatives of their normal substrates. The team also introduced a gene for a transport protein that carries a fluorine-containing starting material, fluoromalonate, into the cell. The enzymes allowed the cells to use the biosynthesis pathway to make fluoromalonyl coenzyme A and convert it to the 2-fluoro-(R)-3-hydroxybutyrate diketide in high yield.
The researchers introduced yet another gene for an enzyme used by many bacteria to make polyhydroxyalkanoates (PHAs) – polyesters used to store carbon and energy. Biodegradable PHAs are used in the production of bioplastics for food packaging and medical implants. The new, genetically engineered microorganisms incorporated the fluorinated diketides into the PHAs, generating polymers containing 5–15 % fluorinated monomers. The bioplastics were less brittle than fluorine-free PHAs. The researchers claim that controlled incorporation of fluorinated monomers could allow for targeted variation of bioplastic properties.
The researchers also hope to use the key component, fluoromalonyl coenzyme A, to produce a range of small fluorinated molecules in living cells for pharmaceutical applications.
With fluorinated molecules having such considerable importance to a wide range of industries, SCI is hosting the Organofluorine Chemistry: Synthetic Methods and Applications symposium in London on 9 February 2018. The conference aims to highlight recent advances in synthetic methodology for the controlled introduction of fluorine into organic molecules, and to showcase its application to alter the structural and physical properties of molecules.
Leading academics from the UK and Europe will present their latest research on the synthesis and application of fluorinated organic molecules, and experienced speakers from the pharmaceutical industry will provide insights into the application of organofluorine compounds to challenging real-world problems. Book your place before 8 December to receive the discounted early bird fee.