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• W4310783921 startingPage "168" @default.
• W4310783921 abstract "Abstract Anaplerosis is an essential feature of metabolism that allows the continuous operation of natural metabolic networks, such as the citric acid cycle, by constantly replenishing drained intermediates. However, this concept has not been applied to synthetic in vitro metabolic networks, thus far. Here we used anaplerotic strategies to directly access the core sequence of the CETCH cycle, a new-to-nature in vitro CO 2 -fixation pathway that features several C 3 –C 5 biosynthetic precursors. We drafted four different anaplerotic modules that use CO 2 to replenish the CETCH cycle’s intermediates and validated our designs by producing 6-deoxyerythronolide B (6-DEB), the C 21 -macrolide backbone of erythromycin. Our best design allowed the carbon-positive synthesis of 6-DEB via 54 enzymatic reactions in vitro at yields comparable to those with isolated 6-DEB polyketide synthase (DEBS). Our work showcases how new-to-nature anaplerotic modules can be designed and tailored to enhance and expand the synthetic capabilities of complex catalytic in vitro reaction networks." @default.
• W4310783921 created "2022-12-17" @default.
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• W4310783921 date "2022-12-05" @default.
• W4310783921 modified "2023-10-10" @default.
• W4310783921 title "Synthetic anaplerotic modules for the direct synthesis of complex molecules from CO2" @default.
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• W4310783921 doi "https://doi.org/10.1038/s41589-022-01179-0" @default.
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• W4310783921 hasPublicationYear "2022" @default.
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