Biosynthesis and Synthetic Biology of Fluorinated Products in Plants

Fluorine is the 13th abundant element in the earth’s crust, but it appears that Mother Nature is unable to efficiently explore fluorine to produce natural organofluorine compounds, and thus only a few are known to date. And due to that, a synthetic approach becomes essential to exploring their benefits. In the last two decades, we have been observing that the development of methods for the introduction of fluorine atoms into organic compounds has become one of the most popular synthetic organic chemistry topics since organofluorine compounds exhibit very interesting physiochemical and biological properties. As a result, these compounds are widely used in the development of pharmaceutical and functional organic compound. However, the introduction of fluorine atoms to organic compounds is very difficult since it is highly sensitive to the type of functional group and substituent, and thus a general and selective fluorination method is not available. Also, due to the inherent properties of fluorinated compounds, functional manipulation of higher analogues is difficult. As a result, synthesizing complex organic compounds for medicinal chemistry becomes a difficult task. Synthetic biology approaches have recently gained popularity as a method for synthesizing complex new organic compounds and of natural product analogues. The concept has also been used to produce organofluorine compounds using natural fluorinase to form the C–F bonds. Thus, activating the silent gene clusters by using protein engineering technology to design a new fluorinase can be used for large-scale manufacture of fluorinated products. Many fluorinated analogues of therapeutically useful drugs have been developed by incorporating fluorinated building blocks into the natural product biosynthetic pathway. Thus, this review summarizes the biosynthesis pathways of a few natural fluorinated organic compounds and few developed strategies for producing fluorinated compounds by using recently discovered fluorinase enzyme and fluoride biosynthesis via synthetic biology. We believe that with continuous advancement of techniques of synthetic biology, the efficiency of biosynthesis of fluorine-containing products will improve, allowing us to investigate the synthesis of complex and even chiral fluorinated compounds.