期刊
SCIENCE
卷 341, 期 6150, 页码 1089-1094出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1242345
关键词
-
资金
- NIH [1S10RR023679-01, S10 RR16634-01, 1 T32 GMO66698, 1 DP2 OD008696, R01 GM087934]
- Gerald K. Branch Predoctoral Fellowship
- UC Cancer Research Council Committee Predoctoral Fellowship
- National Cancer Institute [F32 CA137994]
- UC Berkeley
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.
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