Expanding the Fluorine Chemistry of Living Systems Using Engineered Polyketide Synthase Pathways
Year: 2013
Type: article
Abstract: 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.
Source: Science
Institutions: University of California, Berkeley, Stanford University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Structure, Mechanism, and Engineering of Assembly Line Polyketide Synthases, G275892774, Mechanistic analysis of 6-deoxyerythronolide B synthase, Discovery and mechanistic study of fluorine biochemistry, University of California Berkeley Chemistry-Biology Interface Training Program, G5694097243, 500 MHz NMR SPECTROMETER, 600 MHz NMR Spectrometer for Solution-state NMR, G7564391353, G944161323
OpenAlex ID: W2094478741