Engineered fluorine metabolism and fluoropolymer production in living cells

摘要

Fluorine has become an important element for the design of synthetic molecules used for medicine, agriculture, and materials. Despite the many advantages provided by fluorine for tuning key molecular properties, it is rarely found in natural metabolism. We seek to expand the molecular space available for discovery through development of new biosynthetic strategies that cross synthetic with natural compounds. Towards this goal, we have engineered a microbial host for organofluorine metabolism and have shown that we can achieve production of a diketide, 2-fluoro-3-hydroxybutyrate, at ~50% yield. This fluorinated diketide can be used as a monomer in vivo to produce fluorinated poly(hydroxyalkanoate) (PHA) bioplastics with fluorine substitutions ranging from ~5–15%. This system provides a platform to produce mM flux through the key fluoromalonyl coenzyme A (CoA) building block, offering the potential to generate a broad range of fluorinated small molecule targets in living cells.