Departments of Chemistry and Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA, 94720-1460, USA.
Current address: Department of Chemistry & Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.
Angew Chem Int Ed Engl. 2017 Oct 23;56(44):13637-13640. doi: 10.1002/anie.201706696. Epub 2017 Sep 26.
Fluorine has become an important element for the design of synthetic molecules for use in 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 the development of new biosynthetic strategies that cross synthetic with natural compounds. Towards this goal, we engineered a microbial host for organofluorine metabolism and show that we can achieve the production of the fluorinated diketide 2-fluoro-3-hydroxybutyrate at approximately 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 around 5-15 %. This system provides a platform to produce mm flux through the key fluoromalonyl coenzyme A (CoA) building block, thereby offering the potential to generate a broad range of fluorinated small-molecule targets in living cells.
氟已成为设计用于医学、农业和材料的合成分子的重要元素。尽管氟在调整关键分子性质方面提供了许多优势，但它在天然代谢中很少见。我们试图通过开发新的生物合成策略来扩展可用于发现的分子空间，这些策略将合成与天然化合物相结合。为此，我们设计了一种用于有机氟代谢的微生物宿主，并表明我们可以以约 50%的产率生产氟化二酮酸酯 2-氟-3-羟基丁酸酯。这种氟化二酮酸酯可用作体内单体，以生产具有氟取代基约 5-15%的氟化聚（羟基烷酸酯）（PHA）生物塑料。该系统提供了一个通过关键氟代丙二酰辅酶 A（CoA）构建块产生毫米通量的平台，从而有可能在活细胞中生成广泛的氟化小分子靶标。
