Zhao Yuqiong, Zhang Wenyu, Liu Wen, Tang Zhijun
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Chembiochem. 2025 Jan 14;26(2):e202400751. doi: 10.1002/cbic.202400751. Epub 2024 Nov 11.
Modular type I polyketide synthases (PKSs) are remarkable molecular machines that can synthesize structurally complex polyketide natural products with a wide range of biological activities. In these molecular machines, ketosynthase (KS) domains play a central role, typically by catalyzing decarboxylative Claisen condensation for polyketide chain extension. Noncanonical KS domains with catalytic functions rather than Claisen condensation have increasingly been evidenced, further demonstrating the capability of type I PKSs for structural diversity. This review provides an overview of the reactions involving unusual KS activities, including PKS priming, acyl transfer, Dieckmann condensation, Michael addition, aldol-lactonization bicyclization, C-N bond formation and decarbonylation. Insights into these reactions can deepen the understanding of PKS-based assembly line chemistry and guide the efforts for rational engineering of polyketide-related molecules.
模块化I型聚酮合酶（PKSs）是一类卓越的分子机器，能够合成具有广泛生物活性、结构复杂的聚酮类天然产物。在这些分子机器中，酮合成酶（KS）结构域发挥着核心作用，通常通过催化脱羧克莱森缩合反应来实现聚酮链的延伸。越来越多的证据表明，具有催化功能而非克莱森缩合功能的非典型KS结构域的存在，进一步证明了I型PKSs生成结构多样性的能力。本综述概述了涉及异常KS活性的反应，包括PKS引发、酰基转移、迪克曼缩合、迈克尔加成、醛醇内酯化双环化、C-N键形成和脱羰反应。深入了解这些反应有助于深化对基于PKS的装配线化学的理解，并指导聚酮类相关分子的合理工程设计。
