Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-1460, USA.
Science. 2013 Sep 6;341(6150):1089-94. doi: 10.1126/science.1242345.
Organofluorines represent a rapidly expanding proportion of molecules that are used in pharmaceuticals, diagnostics, agrochemicals, and materials. Despite the prevalence of fluorine in synthetic compounds, the known biological scope is limited to a single pathway that produces fluoroacetate. Here, we demonstrate that this pathway can be exploited as a source of fluorinated building blocks for introduction of fluorine into natural-product scaffolds. Specifically, we have constructed pathways involving two polyketide synthase systems, and we show that fluoroacetate can be used to incorporate fluorine into the polyketide backbone in vitro. We further show that fluorine can be inserted site-selectively and introduced into polyketide products in vivo. These results highlight the prospects for the production of complex fluorinated natural products using synthetic biology.
有机氟化合物在药物、诊断、农用化学品和材料中得到了广泛的应用，其在分子中的占比也在迅速扩大。尽管氟在合成化合物中很常见，但已知的生物作用范围仅限于产生氟乙酸盐的单一途径。在这里，我们证明该途径可以被利用为将氟引入天然产物支架的氟化构建块的来源。具体来说，我们构建了涉及两个聚酮合酶系统的途径，并表明氟乙酸盐可用于在体外将氟掺入聚酮主链中。我们进一步表明，氟可以在体内选择性地插入并引入到聚酮产物中。这些结果突出了使用合成生物学生产复杂氟化天然产物的前景。
