Characterization Of The Polyspecific Transferase Of Murine Type I Fatty Acid Synthase (Fas) And Implications For Polyketide Synthase (Pks) Engineering

<strong>Characterization of the polyspecific transferase of murine type I fatty acid synthase (FAS) and implications for polyketide synthase (PKS) engineering</strong> https://dx.doi.org/10.1021/acschembio.7b00718 <strong>Abstract</strong> Fatty acid synthases (FASs) and polyketide synthases (PKSs) condense acyl compounds to fatty acids and polyketides, respectively. Both, FASs and PKSs, harbor acyltransferases (ATs), which select substrates for condensation by β-ketoacyl synthases (KSs). Here, we present the structural and functional characterization of the polyspecific malonyl/acetyltransferase (MAT) of murine FAS. We assign kinetic constants for the transacylation of the native substrates, acetyl- and malonyl-CoA, and demonstrate the promiscuity of FAS to accept structurally and chemically diverse CoA-esters. X-ray structural data of the KS-MAT didomain in a malonyl-loaded state suggests a MAT-specific role of an active site arginine in transacylation. Owing to its enzymatic properties and its accessibility as a separate domain, MAT of murine FAS may serve as versatile tool for engineering PKSs to provide custom-tailored access to new polyketides that can be applied in antibiotic and antineoplastic therapy. <strong>Raw dataset for protein databank accession code (PDB) 5my0</strong> http://dx.doi.org/10.2210/pdb5my0/pdb