Plant polyketide synthases (PKSs) catalyze iterative decarboxylative condensations of malonyl units (Claisen-type C-C bond formation) with a CoA-linked starter molecule to produce linear chain polyketide intermediates. By Claisen, aldol cyclization, or lactonization, and aromatization, the linear chain polyketide intermediates produce varied unnatural small molecules. In this review, the functions of the known plant PKSs are summarized, and the catalytic mechanisms and applications of plant PKSs in the synthesis of unnatural small molecules are covered. Keywords plant polyketide synthases; unnatural small molecules; combinatorial synthesis; combinatorial biosynthesis 聚酮合酶(Polyketide synthases, PKSs)是生物体中催 化合成大环内酯及芳香环类抗生素、聚烯及聚醚类天然 产物, 还有植物中的间苯三酚、黄酮、蒽醌等多元酚类 化合物的一大类酶的统称. 根据聚酮合酶蛋白结构及催 化机制的不同, 聚酮合酶分为 I, II, III 三种类型. I 型聚 酮合酶(TypeIPKSs)主要来源于微生物中, 由多个功能 模块(modular)组成, 每个模块均包含一套完整的非重复 使用的催化功能域(domain), 程序性的催化完成聚酮类 化合物底物的装载、链的延长修饰、环合及终产物的释 放等一系列步骤(Figure 1A), 催化合成大环内酯类抗生 素(如红霉素)、聚烯及聚醚类化合物 [1] . II 型聚酮合酶 (TypeIIPKSs)是一个多功能酶复合体, 聚酮合成过程中 底物的装载、链的延长修饰、环合及终产物的释放在同 一套可重复使用的功能结构域中完成(Figure 1B). II 型 聚酮合酶也主要来源于微生物中, 主要催化合成芳香环 类抗生素(如四环素)类化合物的生物合成 [2] . III 型聚酮 合酶(Type III PKSs)结构较 I 和 II 型聚酮合酶简单, 不需 要酰基载体蛋白(ACP)的参与, 整个反应由一个同源蛋 白(40～45 kDa)二聚体完成(Figure 1C

4-Coumarate coenzyme A ligase (4CL) and chalcone synthase (CHS), the two pivotal enzymes involved in the biosynthesis of flavonoids were applied to combinatorially synthesize varied unnatural natural products. As result, 25 unnatural natural products including eight flavonoid analogues, 16 4-hydroxy-δ-lactones and one benzalacetone were synthesized by 4CL and CHS. The synthetic methodology would be useful for the construction of library of structurally diverse of small molecules.