Abstract:Sanglifehrin A (SFA) is a spirolactam-conjugated, 22-membered macrolide with remarkable immunosuppressive and antiviral activities. This macrolide is a result of a hybrid polyketide synthase (PKS)nonribosomal peptide synthetase (NRPS) assembly line that utilizes (2S)-2-ethylmalonamyl as a starter unit.Here, we report that the formation and loading of this starter unit in the SFA assembly line involve two unusual enzymatic reactions that occur on a discrete acyl carrier protein (ACP), SfaO. An amide synthetase,… Show more
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