Life Sciences Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Structure. 2010 Jan 13;18(1):94-105. doi: 10.1016/j.str.2009.10.018.
Modular polyketide synthases (PKS) make novel natural products through a series of preprogrammed chemical steps catalyzed by an assembly line of multidomain modules. Each assembly-line step involves unique extension and modification reactions, resulting in tremendous diversity of polyketide products. Dehydratase domains catalyze formation of an alpha,beta-double bond in the nascent polyketide intermediate. We present crystal structures of the four dehydratase domains from the curacin A PKS. The catalytic residues and substrate binding site reside in a tunnel within a single monomer. The positions of the catalytic residues and shape of the substrate tunnel explain how chirality of the substrate hydroxyl group may determine the configuration of the product double bond. Access to the active site may require opening the substrate tunnel, forming an open trench. The arrangement of monomers within the dimer is consistent among PKS dehydratases and differs from that seen in the related mammalian fatty acid synthases.
模块化聚酮合酶（PKS）通过一系列由多域模块组成的流水线催化的预编程化学步骤来制造新型天然产物。每个流水线步骤都涉及独特的延伸和修饰反应，从而导致聚酮产物的巨大多样性。脱水酶结构域催化新生聚酮中间体中α，β-双键的形成。我们展示了来自 curacin A PKS 的四个脱水酶结构域的晶体结构。催化残基和底物结合位点位于单个单体中的一个隧道内。催化残基的位置和底物隧道的形状解释了底物羟基的手性如何决定产物双键的构型。进入活性位点可能需要打开底物隧道，形成一个敞开的沟渠。二聚体中单体的排列在 PKS 脱水酶之间是一致的，与相关的哺乳动物脂肪酸合酶中观察到的不同。
