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.

中文翻译：

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小鼠I型脂肪酸合酶（FAS）的多特异性转移酶的表征及其对聚酮化合物合酶（PKS）工程的意义

脂肪酸合酶（FASs）和聚酮化合物合酶（PKSs）分别将酰基化合物缩合为脂肪酸和聚酮化合物。FAS和PKS都带有酰基转移酶（AT），它们选择通过β-酮酰基合酶（KSs）进行缩合的底物。在这里，我们提出鼠FAS的多特异性丙二酸/乙酰转移酶（MAT）的结构和功能表征。我们为天然底物，乙酰基和丙二酰辅酶A的转酰基作用分配动力学常数，并证明FAS可以接受结构和化学上不同的CoA酯。丙二酰负载状态下KS-MAT二结构域的X射线结构数据表明，活性位点精氨酸在转酰化反应中具有MAT特异性作用。由于其酶学性质和作为单独域的可访问性，