Khosla Chaitan, Tang Yinyan, Chen Alice Y, Schnarr Nathan A, Cane David E
Department of Chemical Engineering, Stanford University, Stanford, California 94305, USA.
Annu Rev Biochem. 2007;76:195-221. doi: 10.1146/annurev.biochem.76.053105.093515.
6-Deoxyerythronolide B, the macrocyclic aglycone of the antibiotic erythromycin, is synthesized by a polyketide synthase (PKS) that has emerged as the prototypical modular megasynthase. A variety of molecular biological, protein chemical, and biosynthetic experiments over the past two decades have yielded insights into its mechanistic features. More recently, high-resolution structural images of portions of the 6-deoxyerythronolide B synthase have provided a platform for interpreting this wealth of biochemical data, while at the same time presenting a fundamentally new basis for the design of more detailed investigations into this remarkable enzyme. For example, the critical roles of domain-domain interactions and nonconserved linkers, as well as large interdomain movements in the structure and function of modular PKSs, have been highlighted. In turn, these insights point the way forward for more sophisticated and efficient biosynthetic engineering of complex polyketide natural products.
6-脱氧红霉内酯B是抗生素红霉素的大环苷元，由聚酮合酶（PKS）合成，该聚酮合酶已成为典型的模块化巨型合酶。在过去二十年中，各种分子生物学、蛋白质化学和生物合成实验已经揭示了其机制特征。最近，6-脱氧红霉内酯B合酶部分的高分辨率结构图像为解释这些丰富的生化数据提供了一个平台，同时为设计对这种非凡酶的更详细研究提供了一个全新的基础。例如，结构域间相互作用和非保守连接子的关键作用，以及模块化聚酮合酶结构和功能中的大的结构域间移动，都得到了强调。反过来，这些见解为复杂聚酮天然产物更复杂、高效的生物合成工程指明了前进的方向。
